T. Bachelet2, L. Couzi1,2,3, C. Martinez1,2,3, J. Visentin1,2,3, G. Guidicelli1, S. Lepreux1,2,3, J.L. Taupin1,2,3, P. Merville1,2,3 1 CHU Bordeaux; 2CTMR, Clinique Saint Augustin; 3Universite de Bordeaux, Bordeaux, France Introduction: At the time of transplantation, solid phase-test tends to replace cell-based test. Flow Cytometry Crossmach (FCXM) may help to recognize pathogenic Donor Specific anti-HLA antibodies (DSA). This approach is not universally used. Here we reported our experience with DSA+FCXM+ transplantations. Patients: We included 175 sensitized Kidney Transplant Recipients (KTR), transplanted with a current negative T-cell Complement Dependent Cytotoxicity crossmatch. FCXM were considered to be positive when Mean Chanel Shift (MCS) > 50 for T cells and MCS > 100 for B cells. Results: Three profiles were identified: 41 DSA+FCXM+, 52 DSA+FCXM, and 82 DSA. Mean Fluorescence Intensity (MFI)-DSA were higher for DSA+FCXM+ (5544  541) than for DSA+FCXM (2581  491), p = 0.02. To prevent antibody-mediated rejection (AMR), some patients received intravenous immunoglobulins (17% DSA, 65% DSA+FCXM, 83% DSA+FCXM+; p < 0.0001), rituximab (1% DSA, 37% DSA+FCXM, 24% DSA+FCXM+; p < 0.0001). Kaplan–Meier estimates over 24 months indicate a higher incidence of acute rejection (AR) and AMR in DSA+FCXM+ group [respectively 7.5% DSA, 16% DSA+FCXM, 40% DSA+FCXM+ for AR and 2.5% DSA, 8% DSA+FCXM, 27.5% DSA+FCXM+ for AMR] and a poorer graft survival [respectively 96% DSA, 94% DSA+FCXM, 85% DSA+FCXM+]. Outcome was not different between DSA and DSA+FCXM groups; as opposed to the DSA+FCXM+ group. Interestingly, only DSA+FCXM+ were still associated with AR in multivariate analysis (OR = 3.2 [1.2–9.3], p = 0.02), after adjustment for MFI-DSA. Conclusion: Taken together, our data confirm the good prognosis of transplantation in sensitized KTR. Solid based tests enable the identification of DSA. Cell-based FCXM test discriminates between pathogenic and nonpathogenic DSA, even better than the MFI-DSA. Refinement of risk stratification through performing prospective FCXM may be useful and guide immunosuppressive strategies.

2 Not attributed.


patients biopsied twice, we observed 4 cases of gDSA positivation and 4 cases of gDSA negativation. 14 patients are gDSA+/AMR suggesting infrahistological diagnostic of AMR confirmed by histological diagnosis of AMR in 9 of the 10 patients biopsied later. Conclusion: gDSA are frequently found in patients with sDSA; they are a witness of the interaction between sDSA and the graft endothelium. They could represent an additional argument for AMR diagnosis and could have a prognosis value that should be confirmed by a prospective study.



Y. Xu-Dubois2,5, J. Peltier4, A. Hertig4,5, I. Brocheriou3, C. Suberbielle1, N. Ouali4, P. Levy2, E. Baugey5, C. Jouanneau5, E. Rondeau4,5 1  APHP Hopital ^ Laboratoire d’Histocompatibilite, Saint Louis; 2Sante Publique; 3  Service d’Anatomo-Pathologie; 4Urgences Nephrologiques & Transplantation  ^ Renale, APHP Hopital Tenon; 5U1155, INSERM, Paris, France Introduction: Antibody-mediated rejection (ABMR) is a leading cause of allograft loss. The efficacy of treatment depends on an accurate diagnosis at an early stage. Sensitive, reliable, especially routinely applicable markers are still lacking. Methods: Using immunohistochemistry, we retrospectively studied the diagnostic value of endothelial-to-mesenchymal transition (EndMT) markers (endothelial expression of vimentin, fascin and hsp47) for ABMR in 53 renal transplant biopsies including 20 ABMR, 24 with T cell-mediated rejection and 9 normal grafts. We validated our results in a second set of 74 non-selective biopsies. Results: EndMT markers were very strongly expressed in the endothelial cells of peritubular capillaries in grafts with ABMR, and absent in normal renal grafts. The level of expression of EndMT markers was significantly associated with capillaritis (q = 0.6, p < 0.0001), glomerulitis (q = 0.5, p = 0.0002), peritubular capillary c4d deposition (EndMT score = 3.44  0.18 vs. 1.8  0.24 for c4d+ or c4d groups, p = 0.0019), but not with i and t scores. In addition, EndMT identified ABMR at an early stage before clinical or histological features of ABMR, as well as C4d-negative ABMR. EndMT markers predicted significantly late (up to 4 years post biopsy) renal graft dysfunction (q = 0.66, p < 0.0001) and proteinuria (q = 0.414, p = 0.023). A prolonged cold ischemia time and a history of delayed graft function were the main risk factors associated with the occurrence of EndMT markers. In the second independent set of 74 biopsies, the level of EndMT marker expression was significantly higher in the patients with DSA than without (1.7 vs. 0.7, p = 0.0065). The diagnostic value of EndMT markers for ABMR was confirmed and showed a sensitivity of 100% and a specificity of 85%. Conclusion: The capillary endothelial activation detected by the expression of EndMT markers is a sensitive and reliable diagnostic tool for ABMR, and predict late allograft function loss.


J. Olagne1,2, A. Parissiadis3, S. Caillard1, N. Froelich3, L. Marcellin2, L. Braun-Parvez1, G. Gautier-Vargas1, F. Heibel1, C. Muller1, P. Perrin1, C. Gachet3, B. Moulin1 1  Service de Nephrologie et Transplantation; 2Service de Pathologie, CHU; 3  Etablissement Francß ais du Sang, Laboratoire d’Histocompatibilite, Strasbourg, France Introduction: Antibody mediated rejection (AMR) is one of the main cause of loss of the kidney transplant. Despite the new BANFF classification, diagnostic difficulties and lack of prognosis factors persist. The detection of intra-graft DSA (gDSA) could be a diagnostic and prognostic tool of AMR. Methodology: We looked for gDSA in 151 kidney graft biopsies from a monocentric, retrospective and transversal cohort of 87 sensitized recipients (sDSA+). gDSA were identified by Luminex SA assay on kidney biopsies eluates. Biopsies were reviewed and classified according to BANFF 2013 classification. Results: On 87 patients, 65 had AMR. 103 biopsies are sDSA+/gDSA+: 19 in HLA class Iand 90 in HLA class II. We note a significant association of gDSA with both acute (p = 0.031) or chronic (p < 0.0001), with AMR histological features, in particular with C4d deposits p < 0.0001) and microcirculation inflammation (p = 0.002). Patients with gDSA+ have a significantly lower graft function (p = 0.045), a higher level of proteinuria (p = 0.09) and a lower renal survival 4 years after the biopsy (p = 0.09). A sDSA MFI > 3500 predicts the gDSA presence with a sensitivity of 70% and a specificity of 82%. Among 40



 S. Reffet, C. Chauvet, O. Thaunat, M. F. Buron, M. Rabeyrin, O. Rouviere, Brunet, R. Cahen, S. Daoud, C. Pouteil-Noble, R. Codas, L. Badet, E. Morelon Hospices Civils de Lyon, Lyon, France Introduction: Rejection or autoimmune recurrence is often difficult to diagnose in the field of pancreas transplantation. The place of pancreas graft biopsy in the management of pancreas transplant recipients is poorly defined. The aim of this study was to assess the contribution of pancreas graft biopsy in our cohort. Methods: All recipients of pancreas transplant, with or without simultaneous kidney transplant, who had a pancreas graft biopsy for cause since 2011 were included. Biopsies were performed under ultrasound or computer tomographic guidance. We analyzed indications, results, concordance with kidney graft biopsies, and complications. Results: Twenty-eight pancreas biopsies were performed in 24 patients. Six (21%) were non adequate. Twenty-one biopsies were performed for suspicion of rejection (increase in serum lipase n = 17, de novo DSA n = 2, kidney graft rejection n = 2). Among them, 14 showed rejection (grade I cell-mediated rejection n = 7, grade II cell-mediated rejection n = 6, antibody-mediated rejection n = 1) and only 3 were normal (4 non adequate). Evolution after treatment was favorable for all patients with grade I cell-mediated rejection. However, 5 out of 6 patients with grade II cell-mediated rejection lost their graft

© 2015 The Authors Transplant International © 2015 European Society for Organ Transplantation, Transplant International 28 (Suppl. 1), 1–19


Abstracts of the 14th Annual Congress of the French Speaking Society of Transplantation within 6 months. Concordance of pancreas biopsy with kidney biopsy in patients having a kidney graft from the same donor was poor (3 of 8). Four biopsies were performed for abnormal oral glucose tolerance test or appearance of autoantibodies. Islets were seen in 3 of these biopsies, without any abnormality. Biopsies for unexplained inflammatory syndrome were normal. There were no complications of biopsies. Conclusion: Pancreas graft biopsy is essential for the diagnosis and prognosis of pancreas rejection and must be performed in every case of increase in serum lipase or de novo DSA. Concordance with kidney biopsy is poor. The place of pancreas biopsy in autoimmune recurrence still has to be evaluated.



M. Redonnet5, A. Belin2, F. Hau6, O. Toutirais3, E. Quelvennec6, B. Le Mauf3, A. Francß ois4, M. Crahes4, M. Galateau1, C. Nafeh5, A. Gay5, K. Blanchart2, G. Babtasi2, P.Y. Litzler5, J.P. Bessou5 1 Service d’Anatomo-pathologie; 2Service de Chirurgie Cardiaque, CHU de Caen; 3EFS de Haute Normandie, Caen; 4Service d’Anatomo-pathologie; 5 Service de chirurgie cardiaque, CHU de Rouen; 6EFS de Haute Normandie, Rouen, France Introduction: In heart transplantation (HTx), de novo DSA is a risk factor for AMR, but a high proportion of patients (pts) with DSA do not develop AMR. The purpose of this study is to test the accuracy of C0 –binding DSA to predict AMR. thods: A cohort of 35 HTx pts from Rouen and Caen University hospitals, Me followed since January 2011, who developed de novo DSA, were tested for C0 – binding DSA on historical sera with DSA MFI > 1500. Test results were compared with AMR occurrence and graft dysfunction and/or chronic rejection. AMR definition was 2011 ISHLT pathological AMR classification. Two assays detecting C0 were used: C1q- and C3d-binding DSA and there results will be compared with AMR occurrence. sults: A first series of 25 HTx pts with de novo DSA were tested with Re the C3d-binding assay. C0 –DSA binding was correlated with AMR (pAMR equal or superior to 1) occurrence with a 77% sensitivity and a 71% specificity (PPV = 83%, NPV = 63%); and was correlated with graft dysfunction and/or chronic rejection with a 79% sensitivity and a 83% specificity (PPV = 92%, NPV = 63%). C1q-binding DSA study is ongoing and will be presented. Conclusion: In HTx pts with de novo DSA, C0 binding seems to be correlated with AMR occurrence and graft dysfunction and/or chronic rejection, and should be tested in at least one serum sample.


Oral communications


J. Olagne2,3, A. Parissiadis5, N. Froelich5, S. Caillard2, L. Marcellin3, E. Epailly1, H. Kremer1, S. Hirschi4, R. Kessler4, B. Moulin2 1  Service de Cardiologie; 2Service de Nephrologie et Transplantation; 3Service de Pathologie; 4Service de Pneumologie, CHU; 5Laboratoire  Etablissement Francß ais du Sang, Strasbourg, France d’Histocompatibilite, Introduction: Antibody mediated rejection (AMR) is one of the causes of organ dysfunction and graft loss. The limited histological features, with a weak sensibility of c4d, make its diagnosis difficult to assess and its prognosis hard to evaluate. The detection of intragraf DSA (gDSA) could be a diagnostic and prognostic tool of AMR. Methodology: We looked for gDSA in 15 biopsies of 7 heart transplant (HT) recipients of whom 6 were sensitized, and 12 biopsies of 10 lung transplant (LT) recipients of whom 7 were sensitized (sDSA+). AMR was defined by graft dysfunction and/or histological features of rejection and sDSA+. gDSA were identified by Luminex SA assay on heart or lung biopsy eluates. Results: In HT recipients, 6 of the 15 biopsies have AMR features and 8 have gDSA. The concordance level between sDSA and gDSA was 60% (6 sDSA+/ gDSA+). None of the gDSA+ patients was sDSA. There is an 80% concordance level between gDSA and rejection (6 gDSA+/RH+, 6 gDSA/ RH). The single case of gDSA/RH+ was due to a very small size of the biopsy in a patient with a low MFI level of sDSA. The 2 cases of gDSA+/RH came from a heart recipient without graft dysfunction. In one of the 2 HT biopsies, gDSA was present 2 months before rejection diagnosis. Among 3 patients who underwent a subsequent biopsy, gDSA disappeared in one case. In LT recipients, 5 cases of AMR were diagnosed among 12 biopsies. The concordance between sDSA and gDSA was 75% (5 sDSA+/gDSA+) and 100% between gDSA and AMR. Among the 7 gDSA cases, 3 cases were cellular rejection (sDSA) and 3 were diagnosed as pneumonia. The 4 gDSA+ patients evolved to chronic humoral rejection (n = 3) and/or death (n = 3). Among the 2 patients biopsied later, we note 1 case of gDSA positivation. Conclusion: gDSA are detected in 86% of AMR+ in HT biopsies and 100% in LT biopsies when patients have DSA in serum. gDSA could represent a witness of the interaction between sDSA and the graft endothelium. They could become a new criteria for AMR diagnosis and could have a prognosis value that should be evaluated in a larger study.



^ 2, C. Lessore2, M. Frimat2, J. Bloch2, A. Lionet2, A. Grunwald2, F. Provot 1 2 A. Tournoy , M. Hazzan , C. Noel2 1 2  CHRU-lille, Laboratoire hemostase; Service de Nephrologie, Lille, France

A. Sicard4,6,7, V. Meas-Yedid8, M. Rabeyrin3, S. Ducreux1, J.Y. Scoazec3, F. Dijoud2, L. Badet5, V. Dubois1, J.C. Olivo-Marin8, E. Morelon4,6,7, O. Thaunat4,6,7 1 EFS; 2Service d’anatomopathologie, Groupement Hospitalier Est; 3Service  d’anatomopathologie; 4Service de Transplantation, Nephrologie et  ^ Immunologie Clinique; 5Service d’urologie et transplantation renale, Hopital Edouard Herriot; 6Unite INSERM U1111; 7Universite Lyon 1, Lyon; 8Unite Analyse d’images quantitative, CNRS URA 2582, Institut Pasteur, Paris, France

Introduction: We compared the efficiency of Immunoglobulin (Ig) removal and their consequences on haesmostasis of 3 different aphresis techniques in order to choose the one with best benefit/risk for our desensitization protocol in kidney transplantation. Materials and Methods: We performed a prospective monocentric observational study to compare plasmatic exchanges by centrifugation (PE), doublefiltration plasmapheresis (DFPP) and immunoadsoprtion (IA). Results: 65 sessions of apheresis were performed in 11 patients, 23 by IA (LiFE-18 Milteniy), 19 in PE (Haemonetics-Terumo) and 21 by DFPP (Plasauto-ASHAi). Plasmatic volume (PV) treated by session was enhanced in IA with an increased IgG removal (PV: 73.1, removal: 70.1% ml/kg) compared to PE (PV: 42 ml/kg; removal 64.1%) and DFPP (PE: 39.7 ml/kg; removal 45.5%). IgA et IgM removal remained higher in PE (IgA 61%, IgM 68%) and DFFP (IgA 52.4%, IgM 65.7%) than IA (IgA58.2%, IgM 51.9%). No bleeding adverse effect was reported. TP was reduced by 55% in PE, 48.1% by DFPP and 9% by IA (p < 0.001); fibrinogen by 65.2% in EP, 55.2% in DFPP and 24% in IA p < 0.001). Activated Cephalin Time was increased by 5.4 times in DFPP, 3.4 in EP and 3.3 times in IA. TCA increased 5.4 times in DFPP; 3.4 times in EP and 3.3 times in IA. Factors II, V and VIII were reduced respectively by 59.47% (EP), 36.8 (DFPP), 18.1% (IA) for factor II, by 63% (EP), 58.5% (DFPP) and 26.9% (IA) for factor V and by 57.3% (DFPP), 62.4% (EP) 19.8% (IA) for factor VIII. Conclusion: IA was associated with a greater PV treated than EP or DFPP. So we couldn’t conclude in a higher capacity to remove IgG in IA. Nevertheless we could confirm a better haemostasis tolerance during IA apheresis. Consequently, we choose this technique for our desensitization protocol.

Introduction: Kidney graft biopsy plays a key role in diagnosis of antibodymediated rejection (AMR), which is the major cause of kidney graft failure. In AMR, the conventional assessment relies on Banff classification which faces limitations in terms of diagnostic accuracy and risk prediction. We have developed a new method of computerized image analysis in order to finely characterize the quality and intensity of graft inflammation. Methods: Among the 69 kidney recipients, who fulfilled the Banff criteria for AMR between 2004 and 2012 at the Lyon University Hospitals, 57 had enough histological samples left for analysis. Double immunohistological stainings were performed with CD31 (capillaries) and respectively CD68 (macrophages), CD3 (T lymphocytes), CD66b (granulocytes), CD20 (B lymphocytes). Computerized image analysis was used to quantify the number of cell of each type in interstitium, glomeruli and peri-tubular capillaries. The ability of DSA to bind C3d was assessed using flow bead assays. Results: 34 patients had C3d+ DSA and 23 had C3d DSA. Banff score for humoral lesions (g + ptc) was similar in the two groups (3.4  1.1 vs. 3.5  1.2, p = 0.65). The number of B and T lymphocytes per 1000 pixels was similar between groups in glomeruli, interstitium and capillaries. Patients with C3d+ DSA had a higher number of monocytes per 1000 pixels in both peritubular capillaries (0.11 vs. 0.04, p = 0.002), glomeruli (0.03 vs. 0.01, p = 0.018) and interstitium (0.13 vs. 0.04, p = 0.004). The number of activated neutrophils (CD66b) in the interstitium was higher in the C3d+ group (0.004 vs. 0.0005, p = 0.02). Conclusion: Using this novel reproducible approach for topological quantification of inflammation, we observed that histopathological features of complement-binding DSA are different from that of non-complement. Additional analyses are currently performed to investigate whether computer-assisted analysis of graft inflammation can stratify the risk of graft loss.




© 2015 The Authors Transplant International © 2015 European Society for Organ Transplantation, Transplant International 28 (Suppl. 1), 1–19

Oral communications 10

Abstracts of the 14th Annual Congress of the French Speaking Society of Transplantation


L. Alechinsky1, B. Barrou1, G. Malaquin2, O. Huot2 1 ^  ere,  Paris; 2Agence de la Biomedecine,  Hopital Pitie Salpetri Saint Denis, France Objective: Despite a growing organ shortage, a significant number of deceased donor kidneys is retrieved from deceased donors but not transplanted (RNTK). The aim of the study was to determine the main causes of refusal and analyze if it was justified or not. Method: This multicenter national study included all RNTK from January 1, 2012 to December 31, 2012. Data were collected from the national database Cristal managed by the Agence de la Biomedecine. Each case was retrospectively analyzed by an urologist expert in transplantation, to determine, if possible, whether the refusal was justified or not. Results: 252 retrieved kidneys (8.8%) were not transplanted. The main reasons for refusal were as follows: 107 vascular causes, (unsuitable artery (95) or vein (12); 48 tumor suspicion, within the graft (17) or at another site (31); pejorative graft biopsy findings (31); and multiple other factors (66). Among suspected tumors, one third were identified as benign. The refusal was due to iatrogenic lesions for 63 kidneys (25%): 29 complete artery section (main artery in 9 and polar artery in 20 cases) 11 venous injuries, 9 incident during cannulation, 6 kidney capsule lacerations, 5 complete ureteral section and 3 hematoma. Retrospective analysis of refusal causes suggested that 63 kidneys (25%) were probably improperly denied, 115 kidneys (46%) were duly turned down. The analysis was not feasible in 74 kidneys (29%), due to improper data collection. Conclusion: A significant proportion of donated kidneys are unduly not transplanted. The solutions to reduce this unnecessary loss of grafts could be (i) the improvement of data collection and transmission, (ii) the evaluation by 2 experts in the field before turning down an organ, 3. an uropathologist on duty for urgent histology 24 h a day.

Methods: A retrospective study of the pediatric CKLTs performed at our institution between 1992 and 2013 was performed. Results are expressed as median [range]. Results: 18 children (9 boys, age 6.7 [1.0–18.6] years, body weight 13 [10– 40] kg) underwent CKLT for PH1 (n = 14), Boichis syndrome (n = 3) and methylmalonic acidemia (n = 1). Induction therapy consisted in anti-thymocyte globuline (N = 4) or basiliximab (N = 14). Hepatic and renal cold ischemia times were 9.4 [5.6–12.4] and 14.4 [9.3–19.6] h, respectively; 12 patients required per-operative dialysis. In the early post-operative period, dialysis was required in 7 patients; the stay in the PICU was 10 [6–29] days. One patient died from cardiovascular disease 10 years after CKLT. No liver graft loss but 6 acute liver rejections were observed whereas 4 kidney grafts were lost (immediate post-operative period, N = 2). Five renal acute rejections were observed. Neither lymphoma nor solid tumor have been observed so far. At last follow-up (6.3 [0–21] years) for patients with functioning renal graft, renal function was 67 [25–103] ml/min per 1.73 m² and SDS for height was 2.3 [7.2; 2.2]. A specific management was applied after CKLT in PH1 patients, namely citrate (n = 14) and hyperhydration (duration 4.0 [0.5–6.0] years). Oxaluria was normalized in 6 patients 3 years after CKLT, but 4 patients still presented with increased oxalaturia 1, 2, 3 and 10 years after Tx. Conclusion: This series confirms the feasibility of pediatric CKLT with encouraging results in the long term, even in the youngest patients. In PH1, the underlying disease burden as assessed by urinary oxalate can persist for months/years, thus requiring specific follow-up and management.



J. Rogier, S. Roullet, F. Cornelis, M. Biais, P. Bioulac, B. Le Bail CHU Bordeaux, Bordeaux, France



K. Kitajima, T. Murakami, I. Koyama, I. Nakajima, S. Fuchinoue Department of Surgery, Kidney Center, Tokyo Women’s Medical University Hospital Introduction: While the short-term results of solitary renal transplantation have improved considerably, favorable long-term outcomes have not yet been obtained because of chronic transplant nephropathy. We reviewed the longterm outcome of renal allografts in patients receiving sequential liver and kidney transplants from a single living donor. Methods: Thirteen patients (3 adults, 10 children) underwent sequential liver (LTx) and kidney (KTx) transplantations from a single living donor between August 1996 and July 2014 at our center. The initial immunosuppressive agents used for the LTx were continued with dose modifications after the successive KTx. Results: KTx was performed between 1.7 and 47.0 months after the LTx. One patient died two months after the KTx because of sepsis. The overall patient survival rate was 92.3% at 10 years. In 11 of 12 remaining patients, the renal allografts were found to be functioning, based on serum creatinine levels, after a mean follow-up period of 87.3 months (5–211 months). Only the first case, transplanted in 1996, exhibited allograft loss 17 years after transplantation because of chronic antibody-mediated rejection. The death-censored renal allograft survival rate at 10 years was 100%, which was better than that of KTx alone (84.9%) in Japan. Overall, only one case of biopsy-proven acute renal rejection requiring intensive treatment occurred within three years of the post-transplant period. The incidence of acute renal rejection was also lower after LTx/KTx than that after KTx alone at our center (8.3% vs. 13.6%, respectively). Conclusions: Immunological protection conferred by the preceding liver allograft may have contributed to the long-term outcome of the renal allograft. In addition, the early suspension of steroid administration thanks to the occurrence of fewer rejection episodes might have contributed to the advancement of normal growth in pediatric transplant patients.



R. Duclaux-Loras1,2, J. Bacchetta1,2, C. Rivet1,2, A. Lachaux1,2, E. Javouhey1,2, O. Boillot2, R. Dubois1,2, B. Ranchin1,2, P. Cochat1,2 1  enfant, Bron; 2Hospices civiles de lyon, Lyon, France Hopital Femme mere Objectives: The experience of pediatric combined kidney/liver transplantation (CKLT) is limited but this strategy is required in specific diseases such as primary hyperoxaluria type 1 (PH1).

Background: Metabolic disorders including liver steatosis are a major health problem all over the world. In liver transplantation, macrovesicular steatosis is probably the most difficult risk factor to appreciate and remains a major cause of graft failure. Computed tomography (CT) is commonly used in cadaveric donors’ management teams to assess donors and to minimize the risk of complications in recipients. The purpose of our study was to validate the use of CT as a semi quantitative assessment of macrovesicular steatosis in cadaveric donors, using liver biopsy as a reference standard. Methods: Our study obtained institutional approval by SRLF ethics committee No. 10-287. A total of 109 cadaveric donors were included between October 2009 and May 2011 (69 men and 40 women, mean age 55  16 years, BMI 26.6  5.0 kg/m2). Brain death was diagnosed according to French law; afterwards liver biopsy and then CT were performed the same day to determine the degree of macrovesicular steatosis. All liver biopsies and CT were analyzed double blinded by one pathologist and one radiologist respectively. For CT, we used the liver to spleen (L/S) attenuation ratio which is a validated method to determine a 30% or greater steatosis in living liver donors. Results: 14 out of 109 biopsies exhibited a macrovesicular steatosis >30%. No bleeding complication was observed. ROC curve was generated for L/S ratio to identify its ability to predict a steatosis >30%. Our results showed a cutoff value of 0.9 for CT L/S with sensitivity of 79% and specificity of 97%. Conclusions: This study is the first performed in cadaveric donors, showing the same results as those found in living liver donors. CT provides high performance in diagnosis of macrovesicular steatosis >30% in cadaveric donors. The use of liver biopsy remains mandatory in donors with more than 30% of steatosis determined by CT to appreciate its severity as well as other histological abnormalities.



A. Schneck, F. Martini, R. Anty, R. Tavana, A. Iannelli, J. Gugenheim CHU de Nice, Nice, France Background: In the selection of marginal liver grafts most transplantation centers use a cut-off of 30% macrovesicular steatosis to define an acceptable risk of non-function. The quantification of steatosis still relies on macroscopic evaluation by the harvesting surgeon with the aid of a parenchymal biopsy, when available. The aim of this study was the creation of a non-invasive model to predict a steatosis degree >30%, based on simple clinical and biochemical markers available at the time of potential liver donor evaluation, in order to avoid futile and expensive procurement proceedings. Methods: Data from 857 morbidly obese patients operated on for bariatric surgery in our center were prospectively collected. Liver biopsies were obtained and patients were divided in two groups according to the degree of steatosis classified as 30% and >30%. Univariate and multivariate analysis were performed in order to identify parameters associated with steatosis >30%.

© 2015 The Authors Transplant International © 2015 European Society for Organ Transplantation, Transplant International 28 (Suppl. 1), 1–19


Abstracts of the 14th Annual Congress of the French Speaking Society of Transplantation Results: Steatosis >30% was found in 55% of the study population. Age, alanine aminotransferase (ALT) and waist circumference were found to be independently associated with steatosis >30%. Combining these parameters we developed a model to predict steatosis >30% with an area under the receiver operating characteristic (AUROC) of 0.78 (95% CI: 0.75–0.81). The best threshold was 0.06 offering a sensitivity of 72% a specificity of 70%. Conclusions: a model combining 3 simples biological parameters can accurately predict steatosis >30% in morbidly obese patients and could be used to better select marginal grafts before activating the procurement proceeding.



J. Baudenon1, D. Anglicheau2, P. Gatault4, I. Etienne3, C. Garrouste1, A.E. Heng1 1 CHU Gabriel Montpied, Clermont Ferrand; 2CHU Necker, Paris; 3CHU Bois Guillaume, Rouen; 4CHU Bretonneau, Tours, France Introduction: In 2013, the disseminated intravascular coagulation (DIC) was diagnosed in 19 of 1504 brain death kidney donors in France. The aim of this study was to evaluate the impact of donor DIC on kidney transplantation (KT). Method: We identified 126 kidney recipients with DIC+ brain death donors between 01/01/1996 and 12/31/2012 in 4 French transplantation centers. They were matched to 126 recipients with DIC donors according to donor age, gender, expanded criteria, transplantation date and center. Results: DIC+ donors had a higher Creatinine than DIC donors (134.5 vs. 90.0 lM, p = 0.001) and received more amines (p = 0.01) and transfusion (85.5 vs. 32.5%, p = 0.001).One and five years kidney survival was 92.7% and 83.5% in DIC+ donors recipients, and 95.3% and 85.2% in DIC donors recipients (p = ns). eGFR median in DIC+ donors recipients and in DIC donors recipients at M3 were 43.3 and 47.76 ml/min (p = 0.09); at M12: 45.48 vs. 48.3 ml/min (p = ns) and at M60: 37.54 vs. 38.56 ml/min (p = ns) respectively. Among recipients whose donor’s creatinine was >133 lM, M3 eGFR medians were 46.5 in DIC+ and 46.1 ml/min in DIC donors recipients (p = ns). Delayed graft function (DGF) was observed in 34.8% in DIC+ vs. 22.7% in DIC (p = 0.04). Blood, platelet and fresh plasma frozen infusion frequency was not different between the two groups. The average period of hospital length of stay was similar in DIC+ (18.3 days) and DIC donors recipients groups (17 d) (p = ns). Discussion: DIC in cadaveric donors is associated with DGF and a tendency to a lower initial eGFR in kidney recipients. This is probably due to kidney damage in DIC+ donors (tubular necrosis, glomerular thrombi . . .). Analysis of the subgroup of DIC+ donors with thrombocytopenia remains to be done. Conclusion: DIC of the donor does not affect graft survival or long-term graft function.



P. Baltzinger4, T. Bahougne4, L. Kessler4, T. Gegot2, M. Greget1,3 ^ Service de chirurgie thoracique, Hopitaux Universitaires; 2Service de ^ pneumologie, Hopitaux Universitaires; 3Service de radiologie, Hopitaux  et nutrition, Hopitaux ^ Universitaires; 4Sevice d’endocrinologien diabete Universitaires, Strasbourg, France 1

Introduction: Cystic fibrosis related-diabetes (CFRD) is a major factor of morbi-mortality in lung transplantation. We report the follow-up of five patients with end-stage cystic fibrosis and severe CFRD who were treated with combined pancreatic islet-lung transplantation. Patients and Method: Bipulmonary bloc and pancreas are procured from the same donor. During the lung transplantation, slet isolation and culture are performed in the laboratory. Two weeks after lung transplantation, the islets are injected by percutaneous transhepatic catheterization of the portal vein under local anesthesia. Immunosuppression associates steroids and basiliximab for induction and then tacrolimus with mycofenolate mofetil and steroids. Results: From October 2011 to May 2014, five CF patients (2 F/3M, age: with respiratory insufficiency 29  5 years, IMC: 17  2 kg/m2) (FEV1:23  3%) and brittle diabetes (diabetes duration: 10  2 years, HbA1c = 8.2  0.7%, insulin requirement = 43  14 IU/day) underwent combined pancreatic islet- lung transplantation with an amount of 4564  2418 Islets Equivalent/kg. Improvement in lung function was observed in five patients with a FEV1 reaching 96%, 75%, 90%, 68% and 85% respectively 30, 22, 15, 6 and 3 months after lung transplantation. The five patients showed immediately islet graft function with an increase in C peptide plasma levels. No complications related to the islet injection were observed. All patients presented an improvement in the metabolic control with a decrease in HbA1c to 6.3  0.2% in absence of hypoglycemic events and a 50% decrease in the exogenous insulin needs.


Oral communications

Conclusion: In CF patients, combined pancreatic islet-lung transplantation restores both pulmonary function and metabolic control. Intra portal islet infusion does not increase the surgical morbidity of the lung transplantation. Further studies are required to evaluate the benefit risk ratio and the long term benefits of combined pancreatic islet-lung transplantation.



P.O. Delpech1,4, C. Billault1, N. Arzouk1, S. Ourahma2, J.L. Golmard3, J. Tourret1, B. Barrou1 1   ^ ere;  Departement Urologie Nephrologie Transplantation, CHU Pitie Salpetri 2   ^ ere;  3Service Biostatistique, Departement d’anesthesie, CHU Pitie Salpetri Paris; 4Service d’Urologie, CHU La Miletrie, Poitiers, France Faced with the shortage of kidney transplants, donation after cardiac death (DCD) is an alternative with a risk of delayed graft function (DGF) and primary nonfunction (PNF) more important but long-term results comparable to deceased donation brain death (DBD). The objective of the study was to evaluate the DCD and identify risk factors for graft loss. This retrospective monocentric study from 2007 to 2013 compared the DCD and DBD with standard criteria donors (SCD) and expanded criteria donors (ECD). The characteristics of donors, transplant and follow-up until 60 months were compared. The survival curves were performed by Kaplan-Meier test, and univariate and multivariate analysis were performed. 476 grafts were studied including 78 DCD, 198 SCD and 141 ECD. The study of serum creatinine level did not show any difference between the DCD and SCD at 5 years but was better than EDC. In DCD group, the transplant waiting times were significantly shorter compared to the SCD (p = 0.025) and EDC groups (p < 0.0001) as well as waiting times on dialysis. The ischemia time, the DGF and HLA incompatibilities were significantly higher in the DCD group (p < 0.0001 respectively), but did not appear to be risk factors for graft loss. The donor age appeared to be a risk factor for graft loss (p = 0.03) and death of recipients (p = 0.004), as well as cardiovascular risk factors. Five-years graft survival was similar in the three groups, but patient survival was better in SCD and DCD groups than in the ECD group (p = 0.0014). DCD kidney transplantatin is a promising source of grafts with better results than EDC, and could increase up to 16–40% the number of donors. It is necessary to respect the protocol criteria established for this type of donors.



H. Knidiri1, A. Laurain1, A. Jeribi1, L. Mendel2, L. Albano1, J. Jourdan1, E. Cassuto1 1 Medico-Surgical Unit of Kidney Transplantation of the University Hospital of Nice; 2Urology Department of the University Hospital of Nice Introduction: The use of expanded criteria (EC) kidneys allows to old recipients, better access to transplantation. The BIGRE protocol witch gives the possibility to patients aged over 65 years to receive two kidneys, with moderate kidney failure, from the same EC donor, is a step to better access to grafts. But, should we continue doing it? Material and Methods: It’s a retrospective, case-control study, comparing dual transplants (DTX) to single transplants (STX) that were undertaken between the first September 2006 and the first September 2013. The matching has been done between the age of the donor and the recipient in each group, in the same 6 months of transplantation. We compare the postoperative complications and functional results observed in the two groups. Data were analyzed using SPSS 16.0. Results: 42 patients (5.4% of transplantation activity in the same period) who received DTX (mean age = 71.7  3.0 years) are matched to 42 patients who received STX (mean age = 70.5  2.8 years). There were no differences in cold ischemia time and delayed graft function. The delay waiting was shorter in the DTX group than the STX group (7.1  3.3 months vs. 13.9  4.6; p < 0.01). The early reinterventions in the DTX group are more important without a statistic difference between the 2 groups. The indication of reoperation in the DTX group was transplantectomy of the second graft for venous thrombosis in three cases of four cases. STX recipients achieved better creatinine clearance at 7 days, 3, 6, and 12 months, although only significantly at 1 month (54.4  19.5 vs. 44.5  15.6 ml/min; p < 0.05). The patient and graft survival at 1 year was the same in the 2 groups. Conclusion: DTX offered good results for graft survival and renal function compared to STX. The easy access to transplantation remains the strong point of the BIGRE protocol, offering better survival and quality of life to old patients with chronic kidney disease. Continuing this activity is a real gain for all patients in kidney graft waiting list.

© 2015 The Authors Transplant International © 2015 European Society for Organ Transplantation, Transplant International 28 (Suppl. 1), 1–19

Oral communications 19

Abstracts of the 14th Annual Congress of the French Speaking Society of Transplantation


D. Bon, M. Glorion, N. Boildieu, F. Seguin, T. Hauet INSERM U1082, Universite de Poitiers, Poitiers Cedex, France Introduction: Evaluation of preservation protocols for organ transplantation is of primary importance regarding donor pool heterogeneity. We previously present NMR metabolomic analysis of preservation solution in the case of kidney. In the same manner, we propose a NMR analysis of bronchoalveolar lavage fluid (BALF) after an ischemia reperfusion sequence. Materials and Methods: Bronchoalveolar lavage fluid (BALF) was collected after 5 h of reperfusion; explantation of the graft and an upper lobectomy was performed. Washing was done directly by instillation of 40 cc of physiological saline in the left upper bronchus. Samples were centrifuged and supernatant kept at 80°C until high resolution NMR acquisition on an Avance 500SB Spectrometer (Bruker) equipped with a 5 mm broadband inverse probe. Three groups of lung preservation protocol were studied: static preservation with Perfadex solution alone, static preservation with Perfadex solution with addition of an oxygen carrier and sham operated lung (N = 5 in each group). Results: In the control lung, the BALF appears to be clean and we found only few metabolites in low concentrations as lactate. We also found in the NMR spectra metabolites from cell release as choline compounds. For sham operated group, all spectra were similar. BALF from lungs preserved with Perfadex alone showed spectra more complex with higher concentrations of lactate, addition of some metabolites aminoacids (valine, alanine) or sugar body (probably dextran-40 from prefadex solution). The last group with lung preserved with perfadex solution with addition of an oxygen carrier showed intermediate NMR profiles with intermediate concentration. The oxygen carrier seems to have a real impact on BALF composition. Conclusion: We proposed descriptive and preliminary results on BALF analysis by NMR with a comparison of two lung preservation protocols versus healthy lung.



J. Tomasi1,2, S. Giraud1,2, J. Danion1,2, G. Allain1,2, P. Corbi1,2, T. Hauet1,2, C. Jayle1,2 1 Cardio-Thoracic Surgery Unit, University Hospital of Poitiers; 2Institut National  de la Sante et de la Recherche Medicale (INSERM) U1082, University Hospital of Poitiers, France Warm lung ischemia and reperfusion injuries in the lung are of great interest in both thoracic and cardiac surgery. During pulmonary transplantation, especially with non-heart beating donors, these lesions can lead to primary graft dysfunction. During cardiopulmonary bypass (CPB), lungs are vascularized only by the bronchial arteries: so lungs are in subtotal warm ischemia. We evaluated whether CPB is a pulmonary ischemia-reperfusion model by studying inflammation and ischemia-reperfusion injuries in the lungs of healthy swine. We compared 3 groups of Large White swine (n = 6): the CPB group, in which CPB was established between the right atrium and the aorta; the sham group, animals underwent the same anesthetical and surgical procedure except CPB. The third group was a total cardio-circulatory arrest group. We evaluated an ischemic time of 120 min and a reperfusion time of 120 min. Hemodynamical datas were collected; blood and tissue samples were harvested for serical, proteomical and transcriptomical analyses. Pulmonary arterial pressure was collapsed in the CPB group compared to sham group resulting in lung warm ischemia. IL-10 was greater in the sham group compared to CPB group at 120 min of reperfusion, and other markers of inflammation (TNFa, IL-6) were similar. We evaluated the HIF-1a pathway, specific of warm ischemia. In lung tissue sample, VEGF protein was increased significantly at 120 min of reperfusion after CPB and 120 min after total cardiac arrest. That model is an accurate model of warm ischemia in the lungs. Results must be completed by further studies to assess the dynamical expression of genes of HIF-1a pathway. IL-10 may play a protective role in ischemiareperfusion injuries in the lungs by counterbalancing the adverse effects of proinflammatory cytokines also expressed. That model may help to study warm ischemia during CPB or either during pulmonary transplantation with the development of non-heart beating donors programs.



E. Pantazi, M. Bejaoui, E. Folch-Puy, J. Rosello´-Catafau  Institut d’Investigacions Biomediques de Barcelona (IIBB), CSIC, Barcelone, Spain Introduction: Cold Ischemia Reperfusion Injury (IRI) remains a major cause of primary dysfunction of liver grafts. Nicotinamide adenine dinucleotide (NAD+)

is a classical coenzyme mediating many redox reactions and its biosynthesis is mediated partially by nicotinamide phosphoribosyl transferase (NAMPT). Also, NAD+ is the requiring cofactor for the activity of Sirtuin 1 (SIRT1). Sirtuins are known to play major roles in protecting against cellular stress and in controlling metabolic pathways. However, the role of SIRT1 in IRI has not yet been elucidated. Here, we investigate SIRT1 implication in orthotopic liver transplantation (OLT) using IGL-1 preservation solution supplemented with an antiischemic drug, trimetazidine (TMZ). Methodology: Livers from Sprague-Dawley male rats were preserved for 8 h in IGL-1 solution enriched or not with TMZ (106 M) and then subjected to OLT (Kamada0 s technique). After 24 h of reperfusion, rats were sacrificed and liver injury (ALT), mitochondrial damage (GLDH), oxidative stress (MDA) and NAD/ NADH levels were determined. SIRT1, ac-p53, ac-FoxO1 (its direct substrates), NAMPT, p-AMPK, autophagy parameters (beclin-1, LCB3), p-mTOR and p70s6K were determined by western blot. Caspase 3 and Tunnel analysis were also performed as liver apoptosis parameters. Results: TMZ in IGL-1 solution reduced liver injury, oxidative stress and mitochondrial damage, as well as increased SIRT1 protein expression levels, NAD+ and NAMPT. SIRT1 overexpression was accompanied by a significant increase in pAMPK, an inhibition of p-mTOR and p70S6K and the subsequent activation of autophagy. SIRT1 activation was consistent with decreased liver apoptosis. Conclusion: We evidenced, for the first time, that SIRT1 exerts a protective effect against IRI associated with rat OLT. Thus, the modulation of this protein could be a useful pharmacological target for the prevention of liver IRI.



R. Thuillier, T. Hauet CHU de Poitiers/Inserm U1082/Universite de Poitiers, Poitiers, France Objectives: Ischemia reperfusion lesions are an unavoidable consequence of organ transplantation. Researching new therapeutics against these require the definition of early mechanisms. The cytoskeleton is composed of 3 types of filaments: microfilaments, intermediate filaments and microtubules. Methods: In an in vitro model using primary human endothelial cells reproducing the conditions of organ preservation, two aspects were explored: 1-function: using pharmaceutical agents to stabilize microfilaments (Jaspakinolide) and microtubules (Taxol), we determined if maintaining the filament structure could decrease cell death; 2-mechanism: to define the determining factor in cytoskeleton alteration, we separated each of the 3 parameters altered during preservation: solution (culture medium versus preservation solution), oxygen (normoxia versus anoxia) and temperature (37 vs. 4°C) Results: (i) Intermediary filaments, made of vimentin in these cells, were unaffected. (ii) Microfilaments showed radical changes: progressive disappearance of the structure replaced by a disorganized array of nodules. (iii) Microtubules almost completely disappeared with time. The results of the first aspect showed that pharmaceutical intervention could indeed preserve fiber structure but did not alter survival. Regarding the second aspect, our study shows that temperature, and not oxygen deprivation or the solution, was the determining factor of the cytoskeleton’s loss of integrity observed during preservation. Conclusion: The impact of preservation on the cytoskeleton highlights the importance of this structure for the development of new therapeutics and the definition of biomarkers of graft quality.



S. Lepape, R. Thuillier, T. Hauet CHU de Poiters/Inserm U1082/Universite de Poitiers, Poitiers, France Objectives: Reseach into new therapeutics against preservation-induced ischemia reperfusion injury (IRI) require the definition of early mechanisms. During a stress, protein maturation mechanisms are altered, inducing an accumulation of misfolded proteins which stimulates the UPR (unfolded protein response) through 3 pathways: IRE1a-XBP1, PERK-eIF2a-ATF4 and ATF6. We studied the activation of the UPR in preservation and its consequences. Methods: We used a porcine model of kidney preservation and an in vitro model of IRI using primary human endothelial cells. Results: In vivo, during pig kidney preservation, we show that each pathway has a specific activation kinetic, suggesting a unique role for each in the response to IRI. In vitro, using specific pharmaceutical agents (STF083010 to inhibit the endoribonuclease IRE1a, Salubrinal to inhibit the dephosphorylation of EIF2S1 and activate PERK-eIF2a-ATF4, AEBSF to inhibit ATF6), we demonstrate that cell survival can be increased through signal modulation between the three UPR branches. Using siRNA, we show that this increase is dependent the ATF6 pathway and the presence of both IRE1a and XBP1. Conclusion: To our knowledge, this is the first study showing the involvement of UPR in IRI physiopathology and the consequences of UPR pathways modulation. Our in vitro data on cell survival suggest the benefits that therapeutics modulating the UPR could bring to improve organ quality and increase the efficacy of transplantation, particularly in the current context of marginal donors with organs more exposed to IRI and the graft quality decrease.

© 2015 The Authors Transplant International © 2015 European Society for Organ Transplantation, Transplant International 28 (Suppl. 1), 1–19


Abstracts of the 14th Annual Congress of the French Speaking Society of Transplantation 24


R. Codas-Duarte2, E. Baulier7, T. Kerforne5, P.O. Delpech6, T. Saintyves6, B. Barrou4, J.P. Tillement8, T. Hauet7, L. Badet3 2 Groupe Hospitalier Edouard Herriot/Hospices civils de Lyon; 3Groupe Hospitalier Edouard Herriot/Hospices civils de Lyon/Inserm U 1082 Poitiers,  ere/Inserm  Lyon; 4Groupe Hospitalier Pitie Salpetri 1082, Paris; 5Centre 6    Hospitalier Universitaire/Departement d’aneshtesie reanimation; CHU de Poitiers; 7CHU de Poitiers/Inserm U1082/Universite de Poitiers; 8Inserm/CHU de Poitiers, Poitiers, France Objective: Trimetazidin (TMZ), a modulator of mitochondrial metabolism, has shown protective properties in several ischemia reperfusion settings. We evaluated TMZ as an additive to preservation solution in a preclinical pig kidney transplantation model of deceased after circulatory death donor (DCD). Methods: Groups of 7 animals were studied: sham; uninephrectomized (left kidney nephrectomy); IC60VIA (preservation with Viaspan); IC60VIA + TMZ10 (Viaspan + 10 mg/l TMZ); IC60VIA + TMZ20 (Viaspan + 20 mg/l TMZ). Kidneys were subjected to 60 min warm ischemia prior to collection and flushing with cold preservation solution. Function recovery, oxidative stress, inflammation and histological lesions were evaluated. Results: Addition of TMZ significantly improved acute kidney function recovery (p < 0.05), particularly the 20 mg/l dose, as evidenced by serum creatinine evaluation. Tubular function as well as urine concentration were significantly improved (p < 0.05) during the first 2 weeks post transplant. Histological analysis at the end of the first week showed a decrease in kidney necrosis lesions and improvement of repair. During this last week, plasma levels of 8 iso-prostane, lipid peroxydation marker, were also decreased in treated groups, particularly in the 20 mg/l group. Plasma levels of proinflammatory cytokines TNF and IL6 were also decreased. Conclusion: Added to the preservation solution in a model of DCD, TMZ limits the main lesion mechanisms of ischemia reperfusion injury. This type of molecule could also be interesting in conditioning regiments such as abdominal normothermic recirculation.



P.O. Delpech3, S. Maiga3, T. Saintyves3, F. Guy5, J.P. Tasu4, J. Roumy3, E. Baulier3, M. Scepi4, M. Dierick2, T. Hauet3, F. Favreau3 2 UGCT-Department of Physics and Astronomy, Ghent University, Ghent, Belgium; 3CHU de Poitiers/Inserm U1082/Universite de Poitiers; 4CHU de Poitiers, Service de Radiologie; 5CNRS INEE UMR 7262, Poitiers, France Objectives: The microvascular network is a major target of ischemia reperfusion. The goal of our study was to characterize kidney cortex vascular remodeling after ischemia reperfusion and define the most affected area. Methods: We used a pig kidney transplantation preclinical model with controlateral nephrectomy in which the graft is preserved 24 h at 4°C in University of Wisconsin solution. 3 months post-transplant, kidneys (n = 5) were studied ex vivo by microtomography and compared to native kidneys (n = 5, Figure 1a). Vascular network morphology and in particular the density and tortuosity of the vascular segments were analyzed in three dimensions. Cortical blood flow was also evaluated, as well as kidney function and tubular lesions. Results: Kidney ischemia reperfusion lead to a decrease in vascular segment volume associated with a rarefaction of small vessels ( 0.5 mmHg/ml/min) or severe histological lesions or other. Before recovery, they were conserved in situ using a Gillot Sonde (GS) or using a Normothermic Regional Circulation (NRC). A dual kidney transplantation (DKT) was performed if RI were between 0.35 and 0.5. We studied the association between RI and donor’s characteristics and functional outcomes. Between 2006 and 2013, there were 46 patients transplanted from uDDCA including 6 DKT. Median follow-up was 48  27.4 months. There were 86.9% Delayed Graft of Function (DGF) and no Primary Non Function (PNF). At 12 months, the mean calculated glomerular filtration rate and inulin clearance were 44.3  14.6 and 45.4  11.6 ml/min/1.73 m² respectively. RI of grafts preserved by GS (n = 29) were significantly higher than those by CRN (n = 17). RI were significantly associated with donor’s sex and creatinine, duration of warm ischemia and of conservation by NRC/GS. The number of post transplant dialysis and the date of function recovery were significantly improved when the RI were 24 h, or donation after cardiac death. UNOS criteria donors were defined as age 60 years or age 50–59 with 2 other risk factors (cerebrovascular accident, hypertension, or serum creatinine >1.5 mg/dl). Pts were randomized to receive CsA or a more intensive (MI) or LI bela regimen. In this post hoc analysis, the UNOS ECD cohort was evaluated for pt and graft survival, cGFR, acute rejection (AR), and a composite end point (EP) of time to death, graft loss or cGFR < 30 ml/min/1.73 m2. Results: In BENEFIT-EXT, 119 MI, 110 LI, and 123 CsA pts were EBV+ and received a UNOS criteria ECD kidney. At month (M) 36, survival with a functioning graft was similar across treatment arms: 95 (80%) MI, 90 (82%) LI, and 94 (76%) CsA. Mean (SD) MDRD cGFR at M36 was 40.0 (26) MI, 39.7 (24) LI, and 26.3 (21) ml/min/1.73 m2 CsA. At M36, AR was 24 (20%) MI, 22 (20%) LI, 18 (15%) CsA. Fewer bela pts reached the composite EP compared with CsA (Figure). Rates of serious adverse events were generally similar across treatment arms. Conclusions: The results of this post hoc analysis of EBV+ recipients of UNOS ECD kidneys in BENEFIT-EXT demonstrate similar pt and graft survival with both bela regimens versus CsA. Renal function was also improved with bela MI and LI despite numerically higher rates of AR, and the rates of the composite EP were lower with bela MI and LI versus CsA. The positive outcomes in this subset of EBV+ pts are consistent with those observed for bela in the overall BENEFIT-EXT population.

© 2015 The Authors Transplant International © 2015 European Society for Organ Transplantation, Transplant International 28 (Suppl. 1), 1–19


Abstracts of the 14th Annual Congress of the French Speaking Society of Transplantation 32


J. Bigot1,3, C. Pilon1,3, A. Aissat2, M. Matignon3,4, J.L. Cohen1,3, P. Grimbert1,3,4 2 1  Hopital Henri Mondor, CIC Biotherapie; INSERM U955 eq 11; 3INSERM   U955 eq 21; 4Hopital Henri Mondor, Service de Nephrologie, Creteil, France Introduction: The so-called regulatory B lymphocytes are involved in selftolerance. Currently, no specific phenotypic or transcriptional markers are identified. In humans, transitional B cells, immature, are defined by phenotypic markers CD24highCD38high. These cells secrete IL-10 and can inhibit the T cell response in vitro. We have shown recently that kidney transplant recipients treated with Belatacept (CTLA4-Ig, co-stimulatory blocking agent) have significantly more CD24highCD38high transitional B cells compared to recipients treated with calcineurin inhibitors (Leibler C et al, AJT. 2014). Here we present the results of the first transcriptomic analysis of this population. Methodology: B cells were obtained from human PBMC by magnetic bead selection. Three populations were sorted by flow cytometry based on CD24 and CD38: transitional CD24highCD38high population was compared with two control populations CD24+CD38 (memory) and CD24intCD38int (mature). A transcriptomic analysis of these three populations was performed by Agilent Whole human genome oligo microarrays. Results: Bioinformatic analysis showed a particular signature in the population of interest CD24highCD38high with around 500 genes up-regulated and 800 genes down-regulated compared to the two control populations. Twelve genes involved in signaling pathways, apoptosis, cell cycle arrest and metalloendopeptidase activity were specifically expressed in the population of interest. Conclusion: Identification of specific candidate genes by flow cytometry may allow us to better characterize the regulatory B cells phenotype and to identify the mechanisms involved in the regulation process.



2  Y. Luque3, D. Anglicheau3, M. Rabant1, R. Clement , H. Kreis3, A. Sartorius3, G. Bollee3, L.H. Noel1, C. Legendre3 1 ^ Anatomie et cytologie pathologiques, Hopital Necker, APHP; 2Pharmacie, ^  ^ Hopital Necker, APHP; 3Service de Transplantation renale adultes, Hopital Necker, APHP, Paris, France

Intravenous immunoglobulins (IVIG) are widely used in kidney transplantation despite the risk of nephrotoxicity, usually attributed to carbohydrate excipients. In this study, we assessed the safety of high-dose IVIG courses without carbohydrate excipients in kidney transplant recipients. A first part of our retrospective study evaluated renal function after 180 highdose (2 g/kg) IVIG courses without carbohydrate excipients delivered to 84 kidney recipients within 3 months after renal transplantation. A second study compared at 3 months and 1 year post-transplant renal function and histology in 50 patients who received IVIG without carbohydrate excipients and in 27 patients who received IVIG containing carbohydrate excipients. According to the RIFLE criteria, no cases of AKI were reported after 180 courses of IVIG without carbohydrate excipient. The two groups who received IVIG, with or without carbohydrate excipient, HAD similar serum creatinine at 3 months and 1 year after transplantation. However, histological analysis of protocol biopsies showed that the absence of carbohydrate excipient was associated with a decreased prevalence of tubular cytoplasmic macrovacuolisation at 3 months (63% vs. 12%, p < 0.0001) and one year (44.4% vs. 6.1%, p < 0.001). The IF/TA score at 3 months and one year was similar in both groups. High-dose IVIg without carbohydrate excipients are safe in the early postransplantation period. The use of products without carbohydrate excipients appears to decrease tubular damage caused by osmotic nephrosis at 3 months and 1 year after transplantation.



18 € Y. Le Meur3, M. Buchler , C. Mousson6, M.C. Moal3, L. Albano10, P. Merville2, S. Caillard16, I. Etienne15, M. Hazzan7, D. Anglicheau11, J.P. Rerolle8, A.E. Heng5, A.E. Thierry12, C. Vignaud14, O. Toupance13, V. Chatelet4, H. Mazouz1, G. Mourad9, N. Kamar17 1 Amiens; 2Bordeaux; 3Brest; 4Caen; 5Clermont; 6Dijon; 7Lille; 8Limoges; 9 Montpellier; 10CHU, Nice; 11Hopital Necker, Paris; 12Poitiers; 13Reims; 14 Rennes; 15Rouen; 16Strasbourg; 17Toulouse; 18CHU, Tours, France

Introduction: In elderly patients receiving a kidney graft from old donors, CNI-free protocols are interesting but expose to the risk of acute rejection. We conducted the Everold study for assessing the benefit of the use of everolimus in old- for-old renal transplantation (recipient and donor >60 years).


Oral communications

Methods: We included 304 patients with low immunological risk that were randomized to the CsA arm (Csa): anti-IL2R induction/CsA/MMF, or the everolimus switch arm (Evs): switch from CsA to everolimus after 6 weeks, or the de novo everolimus arm (Evd): thymoglobulins/everolimus de novo/MMF). In the 3 groups MPA exposure was normalized using MPA AUCs and steroids were withdrawn after 4 months. Results: Patient characteristics were similar in the 3 groups, in particular mean age of the donors and the recipients (68 and 71 years) and cold ischemia time (16 h). We report data of 285/304 patients that completed the study. One year patient survival was identical in the 3 arms (94%). There were 12 graft losses in the Csa arm versus 7 in the Evs arm and 5 in the Evd arm. Delayed graft function (DGF) and particularly severe and prolonged DGF (more than one HD session) were significantly less frequent in the Evd arm. The 12 month biopsy-proven acute rejection rate was not different between groups: Csa 10%, Evs 15%, Evd 7%. Intent to treat analysis showed similar 1 year GFR (MDRD) respectively 34, 37 and 39 ml/min. The discontinuation rate was high in the everolimus groups: Evs 41%, Evd 62% versus Csa 26%, mainly due to adverse events. Lymphoceles, wound healing complications and neutropenia were more frequent in the Evd arm and mouth ulcers in the 2 everolimus groups. Conclusion: Old-for-old renal transplantation provides good patient and graft survival. The 3 arms seems equivalent in terms of clinical outcome at one year however tolerance of everolimus in these populations was poor.



E. Thimonier1, O. Guillaud1, T. Walter1, E. Decullier2, M. Vallin1, O. Boillot1, J. Dumortier1 1 ^ Hopital Edouard Herriot; 2Hospices Civils de Lyon, Unite de Recherche ^ IMER, Lyon, France Clinique, Pole De novo malignancies are a main cause for late death after liver transplantation (LT). Everolimus (ERL) is an immunosuppressive agent with anti-tumoral properties. The aim of the present retrospective study was to identify prognostic factors, including conversion to ERL, for patients presenting non cutaneous de novo solid organ malignancy after LT for alcoholic cirrhosis. The study population consisted in 83 patients (presenting 100 tumours, including 75% of upper aero-digestive tract cancers), among the 398 patients who underwent LT for alcoholic cirrhosis in our centre. After diagnosis, ERL was introduced in 38 patients and calcineurin-inhibitor was discontinued in 64.1% of them. Tumour stage was a significant prognostic factor with a 1-year survival at 82.6% for early stages, 63.4% for intermediate stages (N+) and 27.4% for disseminated diseases (p < 0.001). Associated relative risk factor was 2.202 (95% CI 1.044– 4.644) for intermediate stages and 5.743 (95% CI 2.436–13.541) for metastatic stages. One and 5-year survival was 77.4% and 35.2% in ERL group versus 47.2% and 19.4% in the non-ERL group, respectively (p = 0.003). The relative risk factor for ERL was 0.447 (95% CI 0.257–0.778). Our results strongly suggest that conversion to ERL improves the prognosis of de novo malignancies after LT for alcoholic cirrhosis. Prospective studies are needed to confirm this benefit.



L. Rostaing1, E. Cassuto2, O. Toupance3, C. Legendre4, P. Merville5, Y. Le 10  , Meur6, B. Moulin7, P.F. Westeel8, B. Hurault de Ligny9, A. Lecuyer  e10, E. Rondeau10 S. Quer 1 ^ ^ ^ Hopital de Rangueil, Toulouse; 2Hopital Pasteur, Nice; 3Hopital Maison ^ ^ ^ Blanche, Reims; 4Hopital Necker, Paris; 5Hopital Pellegrin, Bordeaux; 6Hopital ^ ^ La Cavale Blanche, Brest; 7Nouvel Hopital Civil, Strasbourg; 8Hopital Sud, ^ Amiens; 9CHU, Caen; 10Novartis Pharma SAS, Rueil-Malmaison; 11Hopital Tenon, Paris, France Background: CERTITEM has evaluated the effect of everolimus/calcineurin inhibitors free (CNI free) on fibrosis progression and results have been reported at 12 months (M12). Data at M24 have been collected as part of a 6 year post transplantation observational study (C4Ever), setup to evaluate the impact of CNI free versus cyclosporin + mycophenolic acid (CsA + MPA) on the incidence of cancer and major cardiovascular events (MACE) in renal transplant recipients (RTx). Methods: In CERTITEM, patients were randomized into 2 treatment groups at M3: CNI-free and CsA + MPA. Patients who completed the CERTITEM M12 visit were included in C4Ever. Results: At M24, 141 patients were evaluable (67 in CNI free, 74 in CsA + MPA); among those, 36 and 70 patients respectively remained on their randomization treatment. At M24, biopsy proven acute rejection (BPAR) and de novo donor specific antibodies (dnDSA) occurred more frequently in

© 2015 The Authors Transplant International © 2015 European Society for Organ Transplantation, Transplant International 28 (Suppl. 1), 1–19

Oral communications

Abstracts of the 14th Annual Congress of the French Speaking Society of Transplantation

the CNI-free group (31.3 vs. 5.4%, p < 0.001 and 34% vs. 11.6%). The mean eGFR by MDRD4 formula was comparable: 56.9 ml/min in the CNIfree group vs. 52.9 ml/min in the CsA + MPA group, p = 0.54. Independent factors of BPAR at M24 were a positive epithelial to mesenchymal transition status at M12 and the CNI-free group. The incidence of cancer at M24 was 4.5% in the CNI-free group vs. 4.1% in the CsA + MPA group (ns) and MACE 4.5% vs. 5.4% (ns) respectively. Basal or squamous cell cancer occurred in 1 (1.5%) patient in the CNI-free group vs. 3 (4.1%) in the CsA + MPA ns. Death occurred in 2 pts in the CNI-free group versus none in the CsA + MPA group, ns. No graft loss occurred. Safety was comparable in both groups. Conclusion: At M24, an increased incidence of dnDSA was observed in both groups whilst BPAR increased in the CNI free group. A nonsignificant increase in the incidence of MACE was observed in the CsA + MPA group; incidence of cancer was similar. Longer follow up of this population could provide further evidence regarding incidence of cancer and MACE in RTx.

of the facility [University Hospital, reference – General Hospital, OR 0.48 (95% IC 0.24–0.95) – Private, OR 0.39 (95% IC 0.18–0.83)] and the transplant center (P < 0.05). Variability between dialysis centers was reduced after taking into account for their characteristics but was not influenced by patients characteristics. Conclusion: Preemptive registration is associated with dialysis centers, transplant centers, social deprivation, and can be partly explained by disparities in practices. In view of these findings, public health actions should be implemented to facilitate the access to preemptive registration on the waiting list, especially among the most disadvantaged populations.



A. Heng2,3, B. Pereira1, M. Prieto4  Service de biostatistique; 2Service de nephrologie, CHU G Montpied; 3Faculte  de medecine, Universite d’Auvergne, Clermont-Ferrand, France; 4Department of Transplant Surgery, Mayo Clinic, William J. von Liebig Transplant Center, Rochester, MN, USA 1



C. Garrouste1, G. Canaud2, J. Rivalan4, O. Toupance3, F. Martinez2, J. Aniort1, D. Anglicheau2, A.E. Heng1 1 CHU Clermont Ferrand, Clermont Ferrand; 2CHU Necker, Paris; 3CHU Robert  Reims; 4CHU Pontchailloux, Rennes, France Debre, Introduction: In the literature, only 20 cases of adult renal transplant (RT) recipients with recurrent focal segmental glomerulosclerosis (HSF) treated with Rituximab (RTX) were described. We report a series of 14 adults in 4 transplantation units. Patients: Patient characteristics are: 10M and 4F, age 38  15 years, immunosuppressive regimen: Induction (7SAL, 7 anti-IL2R) then calcineurin inhibitors (8CsA, 6Tac) + mycophenolate + steroids. The time between the TR and HSF recurrence was 14.5 [0–247] days. Initial treatment of the recurrence was Plasmapheresis (PTX) + CsAiv + steroids. The RTX was started immediately (n = 5, G1 group) or after failure of initial treatment (n = 6, G2) or weaning failure from PTX (n = 3, G3). Complete remission (CR) is defined as proteinuria 10/mm3 at the time of relapse in the 3 Pts. A repeated course of RTX allowed 2CR in G3. During the 1st year, 10 patients developed severe infections (13 bacterial, 2 viral, 1 parasite). Discussion: The success rate of RTX in our series (10/14) is comparable to that of literature. CD19 > 10/mm3 may be an indicator of HSF relapse after RTX induced remission. Conclusion: In RT recipients with recurrent HSF, Rituximab treatment maybe useful in case of failure of initial treatment (PTX/CsA/steroids) or weaning failure from PTX.



N. Riffaut1, T. Lobbedez1, M. Hazzan3, D. Bertrand4, P.F. Westeel5, G. Launoy2, N. Bouvier1, B. Hurault De Ligny1 1   Nephrologie, CHU Caen; 2U1086 Cancers et Preventions, Inserm, Caen; 3   Nephrologie, CHU Lille, Lille; 4Nephrologie, CHU Rouen, Rouen; 5  € France Nephrologie, CHU Amiens, Salouel, Background: Outcomes are significantly higher when kidney transplantation (KT) is preemptive rather than performed after dialysis. Enrolment on KT waiting list should be considered preemptively as much as possible. This study was carried out to estimate the association between the renal unit and the preemptive registration on the waiting list for first cadaveric KT in a French network of care. Methods: From 2008 to 2012, 1529 adult-patients followed in 49 centers of the French North-West network, and registered on the waiting list for a first cadaveric KT, were included. We used a traditional logistic regression for bivariate analysis, and mixed logistic regression with dialysis center as random-effects term. Results: Of the 1529 patients included in the study, 407 were placed on the waiting list preemptively. In bivariate analysis, cardiovascular disease (CVD), social deprivation score, ownership of the facility and the transplant center were associated with the preemptive registration. The non-adjusted mixed model showed a significant variability across dialysis centers. In multivariate analysis, factors independently associated with preemptive registration were CVD [OR 0.55 (95% IC 0.39–0.76)], social deprivation [OR 0.74 (95% IC 0.57–0.96)], ownership

Introduction: Access to renal transplantation for obese patients is important because survival is significantly better after transplantation than if they remained on dialysis transplant list. Loosing weight before transplant to have a body mass index (BMI) < 30 or 35 is frequently required this weight loss could be more harmful than beneficial. Methods: We have retrospectively studied the data of 893 transplant patients from 01/01/2007 to 31/12/10 in the Mayo Clinic Rochester, USA Data from non obese patients (NO group) were compared with those from patients with an history of obesity (O group). In the O group, dates from patients with a significant weight loss (WL group) were compared to those from obese patient who have not lost weight (NWL group). Significant weight loss is defined as a decrease in weight observed during the time spends on the waiting list of more than 10% of the initial weight. Results: Most patients received a kidney transplant from a living donor, Of the O group (n = 380, 42%), 33% had a BMI > 30 and 17% a BMI > 35 at time of transplantation. In comparison with NO, O patients are older, have more comorbidities (stroke, hypertension and diabetes), warm ischemia time tends to be longer, surgical complications are more frequent. However the patients and grafts survivals do not differ between the two groups. Apart from a greater proportion of African-American in the WL (n = 78), no differences in demographic characteristics were observed between WL and NWL group. No difference in the incidence of surgical or medical complications was seen between the WL and NWL groups. However, the patients survival adjusted for age and comorbidities is better in NWL group first year post transplantation. Conclusion: Weight loss before transplantation in obese do not decrease surgical complications and may be harmful.



C. Cohen1, M. Charbit2, B. Chadefaux-Vekemans3, M. Giral4, V. Garrigue5, M. Kessler6, C. Antoine7, R. Snanoudj1, P. Niaudet2, H. Kreis1, C. Legendre1, A. Servais1 1 Nephrology and Transplantation Department, Necker Hospital; 2Pediatric Nephrology, Necker Hospital; 3Biochemistry B Laboratory, Necker Hospital, Paris; 4Nephrology and Transplantation Department, CHU Nantes; 5 Nephrology and Transplantation Department, CHU Montpellier; 6Nephrology and Transplantation Department, CHU Nancy; 7Nephrology and Transplantation Department, Saint Louis Hospital, Paris, France Cystinosis is a rare lysosomal disorder leading to end stage renal disease (ESRD) in more than 90% of patients before 20 years old. We report outcome of renal transplantation in cystinosis patients. Data were retrospectively analysed in 5 French university centres. A control cohort of 93 patients was constituted, matching to age, graft date, living/deceased donor and center to cystinosis patients. 31 transplantations were performed between 1980 and 2013. Median age at transplantation was 20.4 years (7–36.5). At transplantation, all cystinosis patients had corneal cystine deposits, 3 diabetes and 7 hypothyroidism. At 10 years graft survival was similar between the two groups (86.5 and 72% respectively). After a median follow up of 144 months (6–340), six cystinosis patients (19%) reached ESRD. At the end of follow up, graft survival was better in cystinosis group with 53% of graft survival at 340 months. Cystinosis complications occurred during follow up: diabetes mellitus (n = 4), hypothyroidism (n = 1), liver involvement (n = 1), neurologic involvement (n = 2). Diabetes after transplantation occurred as frequently in cystinosis than in control patients (13% and 5% respectively, p = 0.25), with no differences in term of calcineurin inhibitors treatment during follow-up. Renal transplantation appears to be safe and efficient in cystinosis patient.

© 2015 The Authors Transplant International © 2015 European Society for Organ Transplantation, Transplant International 28 (Suppl. 1), 1–19


Abstracts of the 14th Annual Congress of the French Speaking Society of Transplantation 41


B. Taton1, K. Moreau1, K. Leffondre2, C. Combe1, P. Merville1, L. Couzi1 1   Nephrologie – Dialyse – Transplantation Renale, CHU de Bordeaux; 2  Biostatistique, Institut de Sante Publique d’Epidemiologie et de  Developpement de Bordeaux, Bordeaux, France Introduction: The 1-year estimated glomerular filtration rate (eGFR) and its evolution during the first year after the transplantation are prognostic markers associated with subsequent graft loss. The goal of our study was to evaluate their performance to predict 5-year allograft loss. Patients and Methods: Demographic and immunologic characteristics of kidney donors and recipients, their 1-year eGFR and its slope during the first year computed by linear regression were analysed for each patient who received a first kidney allograft in our center between 1999-01-01 and 2011-0831. Fine & Gray statistics and ROC curves were used to analyse the prognostic impact of all available variables, and the factors which incluenced the slope of eGFR were determined using a linear mixed model. Results: During a mean follow-up period of 65  41.3 months, 114 out of 961 patients lost their graft and 51 died. The only identified independant prognostic factors were the 1-year eGFR (p = 7 9 107) and its slope over the first year (p = 3.5 9 104). However these markers had poor predictive performances: area under ROC curves were 0.68 and 0.66 respectively. Between 1 and 5 year post-transplantation, the sign of the eGFR slope changed for 40.5% of the analysed patients: 27.2% had a negative 1-year eGFR slope but a positive 5-year slope, and 13.3% exhibited a symmetrical pattern. Marginal donors and class 2 alloimmunisation were associated with more negative eGFR slopes. A lower 1-year eGFR and a steeper decreasing eGFR slope were associated with an increased mortality. Discussion: One-year eGFR and its slope during the 1st year post transplantation are the strongest prognostic factors for kidney allograft. Nevertheless, none of them is reliable to predict 5-year allograft survival. The analysis of eGFR trajectories suggests that long-term allograft outcome depends on events which occur later than 1 year post-transplantation and change the eGFR trajectory in 40.5% of patients.



D. Bertrand1, J. Dehay1, J. Ott2, C. Laurent1, B. Moulin2, M. Godin1 1 ^ CHU Rouen Hopital Bois Guillaume, Bois Guillaume; 2CHU Strasbourg, Strasbourg, France nale est une des options the rapeutiques Introduction: La transplantation re nale chronique terminale des patients de la prise en charge de l’insuffisance re   sclerodermiques. Cependant les donnees actuellement disponibles montre rieures aux autres ne phropathies. une survie du patient et du greffon infe thodologie: Un questionnaire a e  te  adresse  a  chaque centre de transMe nale francßais afin de recenser les patients scle rodermiques plantation re  s re naux. Leurs caracte ristiques cliniques et paracliniques ont e te  transplante pertorie es et leurs survies analyse es. re sultats: Trente quatre patients a ^ ge s en moyenne de 52.9 ans (27.7–75.5) Re  ne ficie  de 36 greffes re nales entre 1987 et 2013. L’atteinte re nale ont be     rodermique dans 76.4% des cas. Le initiale etait liee a une crise renale scle lai entre la prise en charge en dialyse et l’inscription sur liste d’attente est de lai moyen avant greffe de de moins de 24 mois dans 76% des cas et le de cours de la greffe on note une seule non fonction 45 mois (5–153 mois). Au de cidive de la maladie) et 5 reprises retarde es de fonction (13.9%). primaire (re  des anticalcineurines dans Le traitement immunosuppresseur a comporte ro€ıdes ont e  te  prescrits dans 89% des cas et arre ^ te s en 92% des cas. Les ste  6 mois dans seulement 36.7% des cas. Les atteintes extramoyenne a nales scle rodermiques restent stables en majorite  au de cours de la greffe. re  1 an, 3 ans, 5 ans et 10 ans est respectivement de La survie des patients a e pour le de  ce s a  100%, 93.8%, 85.7% et 77.1%. La survie du greffon censure 1 an, 3 ans, 5 ans et 10 ans est respectivement de 97.2%, 93.6%, 89.4%, cidive de crise re nale scle rodermique sont 73.3%. Trois suspicions de re es. rapporte s transplantation Conclusion: La survie des patients et des greffons apre nale est excellente dans notre e tude. En l’absence de contre indication extrare nale a  l’inscription sur liste d’attente, la transplantation re nale nous para^ıt re ^tre privile gie e dans cette population. devoir e



Oral communications


T. Kofman1, S. El Rharib1, N. Kamar3, P. Malvezzi2, M. Matignon1, P. Lang1, P. Grimbert1 1  ^  Nephrologie et transplantation, Hopital Henri Mondor, APHP, Creteil; 2  Clinique Universitaire de Nephrologie, CHU Grenoble, Grenoble; 3   Departement de Nephrologie et Transplantation d’Organes, CHU Rangueil, Toulouse, France Introduction: No data are available on the outcome of kidney transplantation in patients with chronic psychosis or bipolar disorder. Materials and Methods: We conducted a retrospective multicenter study from 1989 to 2012 of three French centers with a sole inclusion criterion of renal transplantation with antecedent of bipolar disorder (BD) or progressive chronic psychosis. Our objective was to evaluate the results of kidney transplantation and the development of psychiatric illness. Results: Twenty-three patients (12 men) aged 30.0–73.0 years (median 51.9 years) were included. Six had been diagnosed with schizophrenia, 2 with chronic paranoid schizophrenia (CPS) and 15 with BD. Twenty-two patients were dialyzed at the time of transplantation with a median time on dialysis of 2.5 years (0.8–11.9). After transplantation, 18 (78.3%) patients experienced at least one psychiatric decompensation including 2 immediately after transplantation and 12 (52.1%) were hospitalized in a specialized environment. Twelve (66.6%) of these patients had a BD and 6 (33.3%) schizophrenia or PHC. An attempt of suicide was reported among the patients with BD. Discontinuation of immunosuppressive therapy was noted in four (17.4%) patients (2 BD and 2 schizophrenics) and for three of them, this cessation was the cause of graft loss. At the end of follow-up [median 5.0 years (0.2–17.9)], 8 patients had an episode of acute rejection. The patient survival was 82.6% and graft survival was 78.3% vs. 83.3 and 77.3% respectively in the control group. The median of estimated GFR was 77.5 ml/min/1.73 m² (40–120). Conclusion: We report for the first time the feasibility of kidney transplantation in a population suffering from a severe psychiatric illness. Kidney transplantation is often complicated with psychiatric decompensation justifying an assessment prior to transplantation and post transplantation medical and psychiatric optimal monitoring.



^ V. Quersin, A. Lionet, M. Hazzan, C. Noel, F. Provot  ^ Service de nephrologie, hopital Claude Huriez, Lille, France Primary focal segmental glomerulosclerosis recurrence on a graft: Interest of plasma exchanges and immuno-adsorption – 11 case studies. Introduction: Primary focal segmental glomerulosclerosis (FSGS) is a nephropathy progressing to terminal kidney disease. Recurrence on a graft is common. In order to reduce relapses, plasma exchanges (PE) are proposed. We report our experiences since 2009. Materials and Methods: We prospectively included all patients with primary FSGS who received a kidney transplant since 2009. Immunosuppressive therapy includes an induction (Thymoglobulin), intraveinous cyclosporine, mycophenolate mofetil and corticosteroids. The PE are carried out according to the Niaudet protocol1. If unsuccessful, the PE are stopped and replaced by immuno-adsorption (IA) then Rituximab if proteinuria persists. Results: We included 11 patients (4 men). FSGS on native kidneys occurred as nephrotic syndrom (9/11) mean age was 21 (4 months to 55 years). Evolution time to dialysis was 11 years and 6 months (3 months to 32 years). Two patients were transplanted for the second time after graft loss due to recurrence. Mean follow-up after transplantation was 18 months (38 months). Eight patients had no recurrence with PE. The others received IA with two partial responses and one complete remission. The mean creatinine at 1 year was 122 lM and proteinuria/creatininuria ratio was 1.6 g/g. Conclusion: Intensive EP changed the prognosis of primary FSGS transplant. We report a series of 11 patients with eight successes due to PE. Three patients relapsed, IA permitted partial (2) and complete remission (1).If EP and IA fail, the role of rituximab in the treatment of recurrent FSGS remains to be determined. Reference: 1. Canaud G, Zuber J, Sberro R, Royale V, Anglicheau D, Snanoudj R, et al. Intensive and prolonged treatment of focal and segmental glomerulosclerosis recurrence in adult kidney transplant recipients: a pilot study. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. mai 2009;9(5):1081–6.

© 2015 The Authors Transplant International © 2015 European Society for Organ Transplantation, Transplant International 28 (Suppl. 1), 1–19

Oral communications 45

Abstracts of the 14th Annual Congress of the French Speaking Society of Transplantation


A. Buzancais, I. Szwarc, F. Vetromile, V. Pernin, S. Delmas, V. Garrigue, G. Mourad  Service de Nephrologie et Transplantation, CHU Lapeyronie, Montpellier, France Introduction: The number of patient returning on dialysis after kidney allograft failure (KA) is increasing and little is known about their characteristics. In this study we compared them with the incident patients during the year before the initiation of dialysis. Material and Methods: We collected all the clinical and the biological datas related to the last year before the patients started dialysis in patients who resume dialysis at CHRU from Montpellier between 2008-01-01 and 2012-1231. Results: On 521 patients who began dialysis, 103 were KA patients and 202 were incident. The mean age was 53.6 years in KA patients vs. 63.9 years in incident patients at the time of initiation of dialysis. Hemodialysis was the most used technic (94.2% in KA vs. 90.6%, ns) and the frequency of the initiation of the dialysis for emergency indications was the same in the two groups. KA patients were more registered on the transplant-waiting list (81% vs. 60%, p = 0.001) but had less consultation (2.9 vs. 3.3 consults per patients, p = 0.004). The BMI was lower in KA patients (23 vs. 26.8 kg/m², p < 0.0001). KA patients were more anemic (hemoglobin 9.7 vs. 10.7 g/dl; p < 0.0001) and required a greater EPO dosing (106 vs. 63 ui/kg/sem, p < 0.0001). They were more acidotic (HCO3 16.7 vs. 18.5 mM, p < 0.0001), had lower albumin levels and lower cholecalciferol levels (37.5 vs. 36.9 g/dl, p < 0.0001 and 15.3 vs. 20.6 nmol/ml, p < 0.0001 respectively). The CRP levels were similar. The Charlson’s score was more elevated in incident patients at the start of the dialysis (p < 0.0001). Conclusion: Glomerular filtration rate is decreasing faster in transplanted patients during the year before resuming on dialysis. Anemia is more severe despite the greater medical prescription in EPO and the nutritional state seems to be more precarious.



Y. Lebranchu1, C. Legendre2, P. Merville2, A. Durrbach2, L. Rostaing2, G. Thibault1, G. Paintaud1, S. Quere3, F.D. Giambattista3, M. Buchler1 1 Tours University Hospital, Tours; 2IDEALE Investigators; 3Novartis Pharma SAS, Rueil-Malmaison, France Background: The IL-2 receptor antibody basiliximab (BSX) at a total dose of 40 mg is known to achieve saturation of the CD25 antigen on T-cells (TC) for approximately 5 weeks (W) in kidney transplant patients (KTP) receiving CsA, an inhibitor of IL-2 production. A total BSX dose of 40 mg may be inadequate to achieve CD25 saturation without concomitant CsA. The effect of higher BSX doses in CsA-free patients is unknown. Methods: In a 12-week, randomized, trial of BSX pharmacodynamics, 16 de novo KTP at low immunological risk received BSX at a total dose of 40 mg + CsA (controls, n = 3), 80 mg + CsA (n = 6) or 80 mg + EVR (n = 7), all with mycophenolic acid and steroids. The primary endpoint was the saturation kinetics of CD25 receptors by BSX to W12, measured by the % of CD25+ TC at specified time points and expressed as saturation area under the effect (AUE, W). The AUE to W12 for the % of TCL binding BSX was also studied. Study recruitment ended prematurely due to a high number of biopsy-proven acute rejections (BPAR) in BSX 80 mg + EVR group. Results: Mean [SD] AUE of CD25 saturation was 8.4 [1.6] W for control, 11.1 [1.1] W for BSX 80 mg + CsA, and 9.7 [0.7] W for BSX 80 mg + EVR. Mean [SD] AUE of BSX binding to CD25 receptors was 7.0 [1.8] W, 9.9 [2.2] W and 8.4 [0.8] W, respectively. BPAR occurred in one control patient, one BSX 80 mg + CsA patient and four BSX 80 mg + EVR patients. There were no deaths and one graft loss (control group). One adverse event (AE) with a suspected relation to BSX was reported, in the BSX 80 mg + EVR group (BK virus infection). Conclusion: BSX at a total dose of 80 mg with a CsA-free regimen may achieve similar CD25 saturation to 40 mg with concomitant CsA during the first 3 months post-transplant. Although the total dose of BSX was doubled it did not seem to provide adequate immunosuppression in KTP to prevent early acute rejection when combined with EVR in CsA-free regimen. BSX at a dose of 80 vs. 40 mg does not appear to be associated with increased BSX-related AEs.



E. Bailly1,2, A. Assaqa3, P. Gatault1,2, V. Chabot3, Y. Lebranchu1,2, J.M. 1,2 € Halimi1,2, C. Baron1,2, M. Buchler 1  Equipe UPRES EA 4245, UFR de Medecine, Universite Francß ois Rabelais,  Tours Cedex 1; 2Service de Nephrologie – Immunologie clinique –   Transplantation renale, Centre Hospitalier Regional Universitaire Bretonneau,  etique,  Tours Cedex 9; 3Service d’Histocompatibilite et d’Immunogen EFS Centre Atlantique, Tours, France Background: Anti-HLA antibodies are a major cause of graft loss through acute and chronic antibody-mediated rejection, and a determinant of graft survival. In addition to Fc-dependant effects responsible for antibody dependant cell mediated cytotoxicity and complement-dependant effects, anti-HLA antibodies are also able to alter cell functions by transducing signals. Such mechanisms have mostly been described for activation, proliferation and survival in endothelial and smooth muscle cells, thus participating in allograft vasculopathy. The impact of anti-HLA antibodies on professional antigenpresenting cells is currently unknown. Methods: Setting-up of an in vitro model of human monocyte-derived dendritic cells expressing an HLA-A2 allele and observation of phenotype modifications and cell survival in the presence of monoclonal mouse anti-HLAA2 or anti-pan-MHC class I or II antibodies from BD PharmingenTM. Results: Dendritic cells lipopolysaccharide, TNFa and CD40 ligand-induced maturation was non specifically inhibited by anti-HLA-A2 or anti-pan-MHC class I antibodies, with suspected Fc-dependant effect. With anti-HLA-A2 antibody F(ab)’2 fragments, we observed a moderate increase of maturation markers expression with low titers and a loss of this maturation process with high titers. Immature and mature dendritic cells survival was unaffected while targeting MHC class I. In contrast, we showed the induction of a dose-dependant maturation of dendritic cells and mature dendritic cell apoptosis by anti-pan-MHC class II. Conclusion: The differential effect when triggering MHC class I or class II suggests the possibility of different signaling and regulation pathways.



C. Barjon2, K. Ghazal2, G. Dahlqvist2, Y. Calmus1,2, F. Conti1,2 1  ^ Centre de transplantation hepatique, Hopital Saint Antoine; 2Inserm UMRS  938, Sorbonne Universites UPMC Univ Paris 06, Paris, France Liver transplantation remains the only treatment for terminal liver disease. However, immunosuppressive drugs required for allograft acceptance are intrinsically toxic and may be responsible for severe side effects. Modulating the immune system of the host to induce tolerance of the graft is a promising new approach to reduce or even eliminate non specific immunosuppressive regimen. More particularly, promoting Tregs could be crucial in achieving operational tolerance. Standard immunosuppressive treatments using calcineurin inhibitors such as tacrolimus have been shown to have a deleterious effect on Treg population. On the contrary, reports indicate that mTOR inhibitors may have a positive impact on Tregs and thus could favor the establishment of operational tolerance. Here we present the first randomized prospective clinical study comparing Tregs levels from liver transplanted patients receiving either tacrolimus or everolimus. A total of 30 patients from four centers were monitored. Blood samples were obtained before transplantation, then 1, 3 and 6 months after transplantation. Flow-cytometry immunophenotyping of Tregs was performed using freshly isolated PBMC. Tregs were isolated from PBMC using magnetic sorting to assess their immunosuppressive capacities. Levels of Tregs were significantly reduced after 1 month of standard tacrolimus-based immunosuppressive regimen (p < 0.05). Six months after transplantation, levels of Treg from patients converted to everolimus were significantly higher than patients who remained under tacrolimus treatment (p < 0.02). Additionnally, we observed a strong tendency (p = 0.057) for higher level of Tregs in HCV-infected patients compared to non infected patients. Tregs conserved their suppressive capacities independently of the treatment and the time point. This is the first clinical study to formally demonstrate the positive impact of everolimus on Tregs levels for liver transplanted patients compared to tacrolimus.

© 2015 The Authors Transplant International © 2015 European Society for Organ Transplantation, Transplant International 28 (Suppl. 1), 1–19


Abstracts of the 14th Annual Congress of the French Speaking Society of Transplantation 49


M. Matignon2,4,5, A. Aissat3, C. Grondin4, D. Desvaux1, M. Garrido6,7, Q. Barathon4, D. Saadoun6,7, P. Lang5, J. Cohen2,4, P. Grimbert2,4,5 1 ^ ^ Anatomopathologie, Hopital Henri Mondor, APHP; 2CIC BT 504, Hopital Henri  Mondor, APHP; 3INSERM U955 equipe 11, Universite Paris 12; 4INSERM   ^ U955 equipe 21, Universite Paris 12; 5Nephrologie-Transplantation, Hopital 6  ^  ^ ere,  Departement  Henri Mondor, APHP, Creteil; Hopital Pitie-Salp etri de   erence  Medecine Interne et d’Immunologie Clinique Centre national de ref des  Maladies Autoimmunes et systemiques rares DHU I2B: Inflammation,  Immunopathologie, Biotherapie, UPMC, Paris VI; 7Laboratoire I3:  Immunologie-Immunopathologie-Immunotherapeutique, UMR 7211 (UPMC/ CNRS), U 959 (INSERM) Universite Pierre Marie Curie, Paris 6, Paris, France Introduction: People aged 65 years reach up to 20% of patients listed for a kidney transplant. In an attempt to meet this rapidly increasing demand, organs from so-called expanded criteria donors (ECD) have been used more frequently. Immune response related to immunosenescence in kidney allografts from ECD has not been studied yet in human. Methods: We profiled 43 kidney biopsies samples presented with acute T-cell mediated rejection (Banff 2013) (ACR), 25 from 23 > 50 years-old recipients engrafted with ECD (ECD group) and 18 from 17 < 50 years-old recipients engrafted with optimal donor (control group). We measured relative expression of a pre-specified panel of 18 mRNAs by quantitative RT-PCR assay. IL-17 protein expression in kidney biopsies has been studied by immunohistochemistry (N = 10). Results: Donor and recipient ages were significantly higher in ECD group (donors: 70  9 vs. 37  8 years, p < 0.0001; recipients: 64  8 vs. 36  10 years, p < 0.0001). ACR histology was similar in both groups. Relative expression of IL-17 mRNA, RORgt mRNA and t-bet mRNA were significantly higher in ECD allografts. Immunochemistry confirmed IL-17 protein expression in old recipients engrafted with ECD presented with ACR. In marginal group, IL-17 mRNA expression in kidney biopsies in marginal group was a negative risk factor for ACR treatment response (classified as resistant if the eGFR did not return to within 20% of the baseline within 4 weeks after initiation of antirejection treatment) with eight ACR resistant in IL-17 positive recipients (54%) and no ACR resistant in IL-17 negative recipients (p = 0.01). Conclusion: Th-17 pathway is increased in ACR in >50 years-old recipients engrafted with ECD. So more, presence of IL-17 expression in those kidney allografts represents a negative impact on ACR treatment response.



A. Durrbach2, H. Chavez1, S. Beaudreuil2, E. Nnang-Obada2, H. Francois2, Y. Taoufik1, B. Charpentier2 1  Laboratoire Immunologie, APHP; 2IFRNT, Service de Nephrologie, Le Kremlin Bicetre, France Introduction: In renal transplantation, treatment with Belatacept in non immunized patients is associated with the same rate of graft loss or death, an improved renal function, a reduction of cardiovascular risk compared to cyclosporin A. However, an increased risk of acute cellular rejection was observed without an increased frequency of DSA. We analyzed biomarkers at the day of the transplant, associated with high risk of developing acute rejection in patients treated with belatacept. Methods: 38 patients were included. All had a lymphocyte phenotyping at D0, D15, D30, D90 and D180. Renal biopsy was performed when an increase of 20% of serum creatinine was observed and systematically J365. The analysis of biopsies was made according to Banff classification. All patients received treatment with Simulect, cellcept (2 g/day) and steroids. Patients were randomized to receive Belatacept or cyclosporin A (BMS IM103-100). Results: 38 patients were included. 26 were receiving belatacept and 12 cyclosporine. 8 patients have developed acute rejection during the first year (7 treated with belatacept and 1 with cyclosporine). The rate of CD4, CD8, CD20, CD56 was comparable during transplantation in the 2 groups. In the patient group treated with Belatacept, only the rate of CD4+ CD57+ (7.1% vs. 1.9%, p < 0.03) and the rate of CD4+ CD62L+ CD45RA+ were higher (9.5% vs. 1.3%, p < 0.007) at day 0 in patients receiving belatacept and up who developed rejection. Other lymphocyte populations were comparable. Conclusions: For patients treated with belataceptfor renal transplantion, the presence of CD4+ CD57+ and CD4+ CD45RA+ CD27 is associated with a higher rejection rate. Their presence at high levels may lead to changes in treatment regimens associated with belatacept.



Oral communications


A. Constantinescu1, M. Abbas1, M. Kassem1, C. Gleizes1, V. Schini-Kerth2, I.L. Mitrea3, F. Toti2, L. Kessler1 1 EA7293, Vascular and Tissular Stress in Transplantation, Federation of Translational Medicine of Strasbourg, Faculty of Medicine, University of Strasbourg, Strasbourg; 2UMR7213 CNRS, Laboratory of Biophotonics and Pharmacology, Illkirch, France; 3Department of Parasitology and Parasitic Diseases and Animal Biology, Faculty of Veterinary Medicine,University of Agronomical Sciences and Veterinary Medicine, Bucharest, Romania Background: New-onset diabetes after transplantation (NODAT) is a major complication in transplanted patients. Cellular mechanisms by which two immunosuppressive drugs, Tacrolimus (TAC) and Sirolimus (SIR) alter the pancreatic exocrine and endocrine cell fate and function were examined. Methods: Human exocrine PANC-1, rat endocrine insulin-secreting RIN-m5f cells, and isolated rat islets were submitted to 100 nM TAC or SIR. In cultures, apoptosis was assessed by annexin-5-FITC and propidium iodide staining, expression of Bax and active Caspase-3, and p53 and p21 senescence markers by Western blot. Cell cycle, and SA-beta-galactosidase (SA-b-gal) activity were analyzed by flow cytometry or fluorescence microscopy. Results: In exocrine PANC-1 cells, TAC and SIR increased Bax (3-fold) and cleaved Caspase-3 (5-fold) expression but only TAC induced early apoptosis. Simultaneously, DΨm was decreased, and p53 and p21 were up-regulated (2.5- and 2-fold increase, respectively). Only SIR prompted cell cycle arrest in G1 phase. In endocrine RIN-m5F cells, TAC and SIR increased apoptosis. Only p53 (TAC: 1.8-fold, SIR 1.7-fold) and p21 (TAC: 2.3-fold, SIR: 3.8-fold) were upregulated. Cell cycle arrest was induced only by SIR. The induction of premature senescence in all pancreatic cells and islets was confirmed by SAbeta-galactosidase activity. Conclusions: TAC and SIR can induce pancreatic cell dysfunction, followed by senescence or apoptosis, but differentially alter endocrine and exocrine pancreatic cells.



C. Chen2, A. Koenig2, D. Chartoire2, T. Defrance2, E. Morelon1, O. Thaunat1,2 1 ^ Hopital Edouard-Herriot, service de transplantation et d’immunologie clinique, Hospices civiles de Lyon; 2Inserm U1111, Lyon, France Background: Antibody-mediated rejection (AMR) is the leading cause of kidney transplant failure. Current immunologic dogma predicts that B cells respond to protein antigen (such as HLA molecules) only with the help of CD4+ T cells. Yet, despite progress in T cell immunosuppression, about 10% of patients develop de novo donor-specific antibodies (DSA) during the first year posttransplantation, a time when IS is maximal and observance usually good. In the present project we aimed at determining whether DSA can be generated in the absence of CD4+ T cell help. Methods and Results: We first investigated the importance of CD4+ T cell for naive humoral allogeneic response. B6 mice genetically deficient in CD4+ T cells (MHC II KO mice) or wild type (WT) were used as recipient of a skin graft (alloantigen drainage to lymph node) or a heterotopic hear transplant (drainage to spleen). Donors were HLA A2 transgenic mice, i.e. B6 mice that express human HLA A2 molecule under the murine MHC I promoter. This trick allowed for the monitoring of DSA response with assays routinely used in the clinic (Luminex). While WT recipients, all developed circulating anti-HLA A2 antibodies, no MHCII KO recipients did whatever the location of alloantigen drainage. We then determined whether CD4+ T cell help was dispensable for memory B cells to respond to a second challenge with the alloantigen. Balb (3rd party) or A2-specific memory B cells were purified from the spleen of recipient WT mice, 45 days after the rejection of 2 successive skin grafts. 5 9 106 purified splenic B cells were transferred IV to RAG KO mice that were then transplanted with A2 heart. None of the RAG recipients developed circulating anti-A2 antibodies. Conclusion: CD4+ T cell help is mandatory for the generation of DSA by na€ıve and memory B cells. These results led us to initiate a clinical study evaluating whether the monitoring of circulating CD4+ T cell allow identifying patients at risk for DSA generation.

© 2015 The Authors Transplant International © 2015 European Society for Organ Transplantation, Transplant International 28 (Suppl. 1), 1–19

Oral communications 53

Abstracts of the 14th Annual Congress of the French Speaking Society of Transplantation


S. Naserian, F. Beckerich, M. Leclerc, C. Pilon, P. Grimbert, J.L. Cohen INSERM U955 IMRB Eq21- CIC-BT, Creteil, France Thymus-derived CD4+ CD25+ Foxp3+ regulatory T cells play a pivotal role in the control of alloreactivity. Since their discovery, several reports have shown that Tregs are involved in tolerance induction to allogeneic skin, islet, and heart transplantation as well as in fetal tolerance. In the context of Graft versus host disease (GVHD), we and others have shown that Tregs specific for allogeneic Ag are far more capable of suppressing effector T cells and controlling the GVHD compared to polyclonal Tregs. Surprisingly, in mice, similar approach does not permit to prevent organ rejection. In bone marrow transplantation, due to irradiation of recipient mice, the Teff/Treg ratio is strictly controlled. This is not the case in solid organ transplantation where infusion of therapeutic Tregs, even at high dose remains less represented compared to conventional T cells. Here, we hypothesized that the ratio between Teffs and Tregs should be the main factor for Tregs functionality. To test this hypothesis, ex-vivo expanded donor specific Tregs from B6 mice were used to control B6C3F1 skin graft rejection in B6 WT or B6 CD3-KO recipients. In wild type C57BL/6 recipients graft rejection occurs in 1 week (MST = 7 days). When 2 million donor specific Tregs were added, we did not observe any delay in skin graft rejection. Using CD3KO recipients first we determined that infusion of 1 million CD3+ effector Tcells is enough to induce acute rejection in 9 days. When Tregs were added at a ratio of 1:1, rejection occurred in 17 days (p = 0.0017). Thus, in this very stringent model of skin rejection, controlling the Treg/ Tconv ratio dramatically ameliorates skin graft survival but is not sufficient to fully control the rejection.



M. Chesneau1,3, L. Michel1,2,3, E. Dugast1,2, A. Chenouard1,3, D. Baron1,3, A. Pallier1, J. Durand1,3, F. Braza1,3, P. Guerif2, D.-A. Laplaud1,2,3, J.-P. Soulillou1,2,3, M. Giral1,2,3, N. Degauque1,3, E. Chiffoleau1,3, S. Brouard1,2,3 1  INSERM, UMR 1064; 2CHU de Nantes, ITUN; 3Faculte de Medecine, Universite de Nantes, Nantes, France Whereas a B cell transcriptional profile has been recorded for operationally tolerant kidney graft patients, the role that B cells play in this tolerance has not been reported yet. In this study, we analyze the role of B cells from operationally tolerant patients, healthy volunteers and kidney-transplant recipients with stable graft function on T cell response. Proliferation, apoptosis and type I pro-inflammatory cytokine production by effector CD4+CD25 T cells were measured after anti-CD3/anti-CD28 stimulation with or without autologous B cells. We report that B cells are able to inhibit CD4+CD25 effector T cell response in a dose dependent manner. This effect needs B cells to interact with their T cell targets and acts through a GzmB dependent pathway. Tolerant recipients harbor a higher number of B cells expressing GzmB and displaying a plasma cell-phenotype. Finally, GzmB+ B cell number is dependent on IL-21 and B cells regulate both the number of IL-21+ T cells and IL-21 production, suggesting a negative feedback loop in these patients which increases excessive B cell activation and allows regulation to take place. These data provide novel insights into the characterization of B cell–mediated immunoregulation in tolerance in clinic and show for the first time a potential regulatory role for B cells on effector T cells in blood from patients with operationally tolerant kidney grafts.


Follow-up was 44 months. There was no difference between the 2 groups in the incidence of bacterial infectious complications: respiratory infections: 30.4% vs. 15%, (p = 0.29), urinary infections: 43.4% vs. 25% (p = 0.33), sepsis: 8.7% vs. 8.7%, (p = 1). There was no difference between the 2 groups in the incidence of viral infections: CMV infection: 47.8% vs. 35% (p = 0.53), BKV infection: 17.4% vs. 25%, (p = 0.71). Incidence of Kaposi sarcoma is 8.7% in the HIV group vs. 5% in the control group (p = NS). Genital herpes is more frequent in the HIV group: 26% vs. 0% (p = 0.02). There is no difference in parasitary infections: intestinal cryptosporidiosis: 13.3% vs. 5% (p value: 0.61). Renal function at 3 months, 1 year and 5 years is no different between the 2 groups, also there is no difference in proteinuria (p = NS). 5- year graft survival is: 95.6% in the HIV group vs. 85%, (p: 0.32) and patient survival is 95.6% vs. 100%, (p: 1). Conclusion: Within the limits of the small number of patients and limited follow-up, infectious complications do not seem to be differrent between the HIV- infected and the non HIV- infected renal transplant patients.


J. Noble1,2, P. Gatault1,2, C. Barbet2, H. Longuet2, E. Bailly1,2, L.B. Lakshmi2, C. Gaudy-Graffin3,4, C. Baron1,2, J.-M. Halimi1,2, Y. Lebranchu1,2, M. Buchler1,2 1 EA4245 Cellules Dendritiques et Greffes, Universite Francß ois-Rabelais; 2  Service de nephrologie et Immunologie Clinique, CHRU de Tours; 3  Laboratoire de bacteriologie et virologie, CHRU de Tours; 4Institut National de   la Sante et de la Recherche Medicale U966, Tours, France Cytomegalovirus (CMV) is associated with an increase of morbidity and mortality after transplantation. Use of Polymerase Chain Reaction (PCR) has been recommended to diagnosis and/or monitoring of CMV infection. Nevertheless the PCR value threshold to start treatment has not yet been defined. Material and Methods: We included all kidney recipients between 05/2012 and 07/2013 in this retrospective monocenter study. CMV PCR (whole blood, threshold = 1.79 log, Abbottâ RealTime CMV) was performed weekly during the first 4 months after transplantation and then monthly during one year except for low risk patients (DR). Prophylaxis (valganciclovir) was given for 3 months for R+ and 6 months for D+R. All patients with at least one positive PCR were included in our analysis. Curative treatment (ganciclovir iv or oral valganciclovir) was started in case of high CMV load (>4 log) and/or clinical/ biological abnormalities associated with positive CMV DNA load (whatever the level). We assessed indications and incidence of curative treatment. Results were expressed as mean  SD. Results: During the 14-month period, a positive CMV viremia using PCR occurred in 59/140 patients after 6.4  5.2 months (5 patients under prophylaxis). Twenty seven (45%) received a treatment (55.5% D+R; 33.3% DR+; 11.1% D+R+). Within these 27 patients, 16 (59%) were treated because of a PCR level higher than 4 log whereas the others were treated because of clinical and/or biological abnormalities associated with positive CMV DNAemia. Thirty two patients (55%) were not treated (50% D+R+; 40.6% DR+; 6.25% D+R; 3.12% DR). Interestingly, 29/32 (87.8%) non-treated patients had spontaneous undetectable CMV load after two controls (15.3% in the treated group, p < 0.0001). No further positive CMV PCR load was observed during the follow-up in these patients. Conclusion: We suggest that a “wait-and-see” attitude may be indicated for patients with low positive CMV load (threshold < 4log on whole blood) in the absence of clinical or biological abnormalities. Keywords: Cytomegalovirus, Kidney transplantation, PCR.


O. Ailioaie, N. Arzouk, M.A. Valantin, J. Tourret, S. Ourahma, L. Mercadal, D. Szumilak, H. Benalia, B. Barrou Hopital Pitie Salpetriere, Paris, France Introduction: The aim of this study is to evaluate the incidence and the type of infectious complications and graft and patient survival in HIV- infected renal transplant patients thods: Retrospective evaluation of prospectively gathered data, between Me January 2004 and June 2014. Only the infectious complications that needed hospitalisation were studied. Results: We have studied 23 renal transplant patients infected by HIV and compared them with 20 renal transplant patients non-infected by HIV. All patients had the same induction therapy (anti IL-2). The groups were matched for age, sex and race.



1,2 € , C. Forconi2, R. Guibon2, Y. Lebranchu2, J.M. J. Noble1,2, M. Buchler Halimi1,2, C. Baron1,2, P. Gatault1 1 CHU; 2EA 4245, Universite Francß ois-Rabelais, Tours, France

Introduction: Cytomegalovirus (CMV) infection is associated in solid organ transplantation with increased morbidity and mortality. We have recently shown that CMV seropositivity of the donor (D+) is an independent risk factor for renal graft loss. IThe purpose of this study was to assess CMV specific CD8 T-cell response in D+ patients compared to DR+. Methods: Fifty-two kidney transplant patients grafted between January 2009 and December 2011 in Tours and expressing either HLA A2 or B7 were identified. Further analyses performed: numbers of anti-CMV CD8 T-cell (PE-conjugated CMVpp65-dextramers), percentage of numbers anti-pp65 CD8 T-cell with TEMRA phenotype (CCR7-neg and CD45RA-pos) and the response to pp65 peptide

© 2015 The Authors Transplant International © 2015 European Society for Organ Transplantation, Transplant International 28 (Suppl. 1), 1–19


Abstracts of the 14th Annual Congress of the French Speaking Society of Transplantation (TNF-a, IFN-c and granzyme B) measured by ELISpot. Results are expressed as mean  SD. Mann–Whitney test was applied for group comparison. Results: Today, 39 patients (29 D+ and 10 DR+) were included. Mean follow-up was 45  11.7 months. Number of anti-CMV CD8 T cells seems increased in D+ group compared to DR+ group (12 223  22 625 vs. 2967  4374 respectively, p = 0.26). However, D+ as compared to DR+ patients had a higher anti pp65 immune response as assessed for TNF-a (13 904  13 234 vs. 2520  3215 p = 0.00026), INF-c (12 653  14 193 vs. 2218  4069, p = 0.0019), and granzyme B (3387  5423 vs. 275  367, p = 0.0024). Numbers of CMV specific TEMRA cells (dextramer+/CCR7/ CD45RA+) were similar between the two groups. Conclusion: This study indicates that receiving a kidney from a CMV infected donor durably affects the long term anti-CMV response. This may suggest recurrent CMV replication episodes inside the graft.



J. Sayegh3, J. Demiselle3, C. Onno3, J. Picquet2, T. Culty4, R. Le Gall1, J.F. Subra3, J.F. Augusto3 1 2    Anesthesie-R eanimation; Chirurgie vasculaire; 3Nephrologie-DialyseTransplantation; 4Urologie, CHU Angers, Angers, France Introduction: Recently, a link between hypogammaglobulinemia (HGG) and infection has been demonstrated in kidney transplant recipients. A metaanalysis has suggested the benefit of IgIV administration. However, these studies have analyzed all type of infections regardless their severity. In our study, we analyzed the relationship between HGG and the risk of severe infection. Methods: We conducted a monocentric cohort study (kidney graft recipients between 2007 and 2013). Ig subtypes (IgG, IgM, IgA) were available prospectively at day 15 (D15), month 6 (M6), M12 posttransplant. Two posttransplant periods were distinguished: P1 (D15-M6) and P2 (M6-M12). Two different persons blinded to each other retrospectively retrieved infectious events from medical records. Results: The study included 189/315 patients with available Ig determination at D15. IgG HGG was observed in 62% and 37% of patients at D15 and M6 respectively. Risk factors (RF) for HGG at D15 were age (OR 1.03) and past history of glomerulonephritis (OR 2.97) in multivariate analysis. RF for HGG at M6 were age (OR 1.03), HGG at D15 (OR 3.49) and acute rejection (OR 4.45) in both uni and multivariate analysis. Most infections occurred during P1 (n = 70). RF of all type of infections between D15 and M24 were age (HR 1.04) and previous transplantation (HR 2.07). Basiliximab induction (HR 0.47) was associated with lower infection risk. Survival free all type infection, bacterial infection and viral infection was not different between patients with or without HGG at D15. Finally, the frequency of infections at P1 and P2 was not different between patients with or without HGG. Conclusion: Our study does not support a link between HGG and severe infection post renal transplantation. The use of IgIV in order to minimize the risk of severe infections in kidney transplant recipients with HGG needs to be evaluated in prospective studies.



A. Rauline1, B. Hurault De Ligny1, F. Comoz3, N. Riffaut1, J. Dina2, T. Lobbedez1, V. Chatelet1, N. Bouvier1 1  Service de Nephrologie – Dialyse – Transplantation; 2Service de Virologie, 3 ^ de Nacre, CHU Clemenceau; Service d’Anatomo-pathologie, CHU Cote Caen, France Background: BK virus is an emerging pathogen in kidney transplant recipients, and often leads to poor graft outcomes. Immunosuppression (IS) reduction is mainly performed in case of BK viremia (BKv), with the risk of acute cellular rejection (ACR). Methods: We retrospectively analyzed 32 kidney recipients with BK viremia from 2006 to 2011. Among them, 34% had ACR after reduction of IS. The aim of this study was to compare patients who had ACR (ACR+, n = 11) with those who had not (ACR, n = 21). Results: ACR occurred in a median time of 18 (10–29) weeks after IS reduction. ACR+ patients had lower glomerular filtration rate at the 1st BKv detection compared to ACR patients: 29 (22–39) vs. 42 (32–53) ml/min/ 1.73 m2 (p < 0.01). The area under the curve of mycophenolic acid (AUCMPA) was 17  11 in ACR+ group vs. 29  11 mg h/l in ACR group (p < 0.05) with a 26.5 mg h/l threshold evaluated by ROC equation below which ACR risk increased. No patient treated with leflunomide developed ACR (n = 3). BKv was still present in 6/11 patients when ACR occurred. ACR were treated with steroid pulses. After a 5  1.6 year mean follow-up, graft and


Oral communications

patient survivals were lower in ACR+ patients compared to ACR patients (respectively 45% and 73% vs. 90% and 90%). Conclusions: ACR must be considered as a serious event after IS reduction in transplant recipients with BKv. Graft dysfunction and AUCMPA < 26.5 mg h/l seem associated with higher risk of ACR. Use of leflunomide remains to be defined: at early BKv stage if an AUCMPA < 26.5 mg h/l is needed to obtain viral clearance or as an adjunctive ACR treatment.



V. Leroy2, J. Dumortier4, A. Coilly14, M. Sebagh14, L. Fougerou-Leurent11, S. Radenne3, D. Botta5, F. Durand1, C. Silvain10, P. Lebray8, P. Houssel-Debry11, N. Kamar12, L. D’alteroche13, Y. Calmus9, I. Bertucci7, A. Diallo7, G.P.  14 Pageaux6, J.C. Duclos-Vallee 1 Hoˆpital Beaujon, Clichy; 2Hoˆpital Michallon, La Tronche; 3Hoˆpital de la CroixRousse; 4Hoˆpital Edouard Herriot, Lyon; 5Hoˆpital de la Conception, Marseille; 6  ^ ere;  9Hoˆpital Hoˆpital Saint-Eloi, Montpellier; 7ANRS; 8Hoˆpital La Pitie-Salp etri St-Antoine, Paris; 10Hoˆpital Poitiers, Poitiers; 11Hoˆpital Pontchaillou, Rennes; 12 Hoˆpital Rangueil, Toulouse; 13Hoˆpital Trousseau, Tours; 14Hoˆpital Paul Brousse, Villejuif, France Introduction: Fibrosing cholestatic hepatitis (FCH) is a rare but severe form of HCV-recurrence following liver transplantation (LT) leading to poor short term survival. Therapeutic options are limited. Study aims were to assess efficacy and tolerance of sofosbuvir (SOF) and daclatasvir (DCV)-based regimens in this setting. Methods: The CUPILT study is a prospective nationwide cohort including patients with HCV-recurrence following LT treated by new antivirals. The present work focused on 21 patients diagnosed with FCH and included between October 2013 and February 2014. FCH diagnosis was based on strict criteria including histological review by an expert pathologist. Treatment regimens were prescribed at investigator’s discretion. Results: FCH was diagnosed after a median duration of 6 months [range 1– 18] following LT and therapy started at 10 months [2–38] post LT. Features of patients at W0 were: median age: 53 years [36–67], men: 81%, G1: 76%, bilirubin: 6.0 mg/dl [0.6–19]. Ascites was observed in 8 (38%) patients. The following regimens were used: Peg-IFNa + SOF + RBV (n = 2), SOF + RBV (n = 6), SOF + DCV (n = 1) and SOF + DCV + RBV (n = 12) for 24 weeks. All patients were alive without re-transplantation at W12. At W12, 20 (95%) patients had HCV RNA

Abstracts of the 14th Annual Congress of the French Speaking Society of Transplantation, 2-5 december, 2014, Caen, France.

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